Children's visual acuity tests without professional supervision: a prospective repeated measures study.

BACKGROUND: Home visual acuity tests could ease pressure on ophthalmic services by facilitating remote review of patients. Home tests may have further utility in giving service users frequent updates of vision outcomes during therapy, identifying vision problems in an asymptomatic population, and engaging stakeholders in therapy. METHODS: Children attending outpatient clinics had visual acuity measured 3 times at the same appointment: Once by a registered orthoptist per clinical protocols, once by an orthoptist using a tablet-based visual acuity test (iSight Test Pro, Kay Pictures), and once by an unsupervised parent/carer using the tablet-based test. RESULTS: In total, 42 children were recruited to the study. The mean age was 5.6 years (range 3.3 to 9.3 years). Median and interquartile ranges (IQR) for clinical standard, orthoptic-led and parent/carer-led iSight Test Pro visual acuity measurements were 0.155 (0.18 IQR), 0.180 (0.26 IQR), and 0.300 (0.33 IQR) logMAR respectively. The iSight Test Pro in the hands of parents/carers was significantly different from the standard of care measurements (P = 0.008). In the hands of orthoptists. There was no significant difference between orthoptists using the iSight Test Pro and standard of care (P = 0.289), nor between orthoptist iSight Test Pro and parents/carer iSight Test Pro measurements (P = 0.108). CONCLUSION: This technique of unsupervised visual acuity measures for children is not comparable to clinical measures and is unlikely to be valuable to clinical decision making. Future work should focus on improving the accuracy of the test through better training, equipment/software or supervision/support.

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.

Evaluating the effectiveness of abbreviated breast MRI (abMRI) interpretation training for mammogram readers: a multi-centre study assessing diagnostic performance, using an enriched dataset.

BACKGROUND: Abbreviated breast MRI (abMRI) is being introduced in breast screening trials and clinical practice, particularly for women with dense breasts. Upscaling abMRI provision requires the workforce of mammogram readers to learn to effectively interpret abMRI. The purpose of this study was to examine the diagnostic accuracy of mammogram readers to interpret abMRI after a single day of standardised small-group training and to compare diagnostic performance of mammogram readers experienced in full-protocol breast MRI (fpMRI) interpretation (Group 1) with that of those without fpMRI interpretation experience (Group 2). METHODS: Mammogram readers were recruited from six NHS Breast Screening Programme sites. Small-group hands-on workstation training was provided, with subsequent prospective, independent, blinded interpretation of an enriched dataset with known outcome. A simplified form of abMRI (first post-contrast subtracted images (FAST MRI), displayed as maximum-intensity projection (MIP) and subtracted slice stack) was used. Per-breast and per-lesion diagnostic accuracy analysis was undertaken, with comparison across groups, and double-reading simulation of a consecutive screening subset. RESULTS: 37 readers (Group 1: 17, Group 2: 20) completed the reading task of 125 scans (250 breasts) (total = 9250 reads). Overall sensitivity was 86% (95% confidence interval (CI) 84-87%; 1776/2072) and specificity 86% (95%CI 85-86%; 6140/7178). Group 1 showed significantly higher sensitivity (843/952; 89%; 95%CI 86-91%) and higher specificity (2957/3298; 90%; 95%CI 89-91%) than Group 2 (sensitivity = 83%; 95%CI 81-85% (933/1120) p < 0.0001; specificity = 82%; 95%CI 81-83% (3183/3880) p < 0.0001). Inter-reader agreement was higher for Group 1 (kappa = 0.73; 95%CI 0.68-0.79) than for Group 2 (kappa = 0.51; 95%CI 0.45-0.56). Specificity improved for Group 2, from the first 55 cases (81%) to the remaining 70 (83%) (p = 0.02) but not for Group 1 (90-89% p = 0.44), whereas sensitivity remained consistent for both Group 1 (88-89%) and Group 2 (83-84%). CONCLUSIONS: Single-day abMRI interpretation training for mammogram readers achieved an overall diagnostic performance within benchmarks published for fpMRI but was insufficient for diagnostic accuracy of mammogram readers new to breast MRI to match that of experienced fpMRI readers. Novice MRI reader performance improved during the reading task, suggesting that additional training could further narrow this performance gap.

"Real-world" radiomics from multi-vendor MRI: an original retrospective study on the prediction of nodal status and disease survival in breast cancer, as an exemplar to promote discussion of the wider issues.

BACKGROUND: Most MRI radiomics studies to date, even multi-centre ones, have used "pure" datasets deliberately accrued from single-vendor, single-field-strength scanners. This does not reflect aspirations for the ultimate generalisability of AI models. We therefore investigated the development of a radiomics signature from heterogeneous data originating on six different imaging platforms, for a breast cancer exemplar, in order to provide input into future discussions of the viability of radiomics in "real-world" scenarios where image data are not controlled by specific trial protocols but reflective of routine clinical practice. METHODS: One hundred fifty-six patients with pathologically proven breast cancer underwent multi-contrast MRI prior to neoadjuvant chemotherapy and/or surgery. From these, 92 patients were identified for whom T2-weighted, diffusion-weighted and contrast-enhanced T1-weighted sequences were available, as well as key clinicopathological variables. Regions-of-interest were drawn on the above image types and, from these, semantic and calculated radiomics features were derived. Classification models using a variety of methods, both with and without recursive feature elimination, were developed to predict pathological nodal status. Separately, we applied the same methods to analyse the information carried by the radiomic features regarding the originating scanner type and field strength. Repeated, ten-fold cross-validation was employed to verify the results. In parallel work, survival modelling was performed using random survival forests. RESULTS: Prediction of nodal status yielded mean cross-validated AUC values of 0.735 ± 0.15 (SD) for clinical variables alone, 0.673 ± 0.16 (SD) for radiomic features only, and 0.764 ± 0.16 (SD) for radiomics and clinical features together. Prediction of scanner platform from the radiomics features yielded extremely high values of AUC between 0.91 and 1 for the different classes examined indicating the presence of confounding features for the nodal status classification task. Survival analysis, gave out-of-bag prediction errors of 19.3% (clinical features only), 36.9-51.8% (radiomic features from different combinations of image contrasts), and 26.7-35.6% (clinical plus radiomics features). CONCLUSIONS: Radiomic classification models whose predictive ability was consistent with previous single-vendor, single-field strength studies have been obtained from multi-vendor, multi-field-strength data, despite clear confounding information being present. However, our sample size was too small to obtain useful survival modelling results.

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.

Correction to: Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

The article Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions), written by Christoph J Rageth, Elizabeth AM O'Flynn, Katja Pinker, Rahel A Kubik-Huch, Alexander Mundinger, Thomas Decker, Christoph Tausch, Florian Dammann, Pascal A. Baltzer, Eva Maria Fallenberg, Maria P Foschini, Sophie Dellas, Michael Knauer, Caroline Malhaire, Martin Sonnenschein, Andreas Boos, Elisabeth Morris, Zsuzsanna Varga, was originally published electronically on the publisher's internet portal (currently SpringerLink) on November 30, 2018 without open access.

Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

PURPOSE: The second International Consensus Conference on B3 lesions was held in Zurich, Switzerland, in March 2018, organized by the International Breast Ultrasound School to re-evaluate the consensus recommendations. METHODS: This study (1) evaluated how management recommendations of the first Zurich Consensus Conference of 2016 on B3 lesions had influenced daily practice and (2) reviewed current literature towards recommendations to biopsy. RESULTS: In 2018, the consensus recommendations for management of B3 lesions remained almost unchanged: For flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL) and radial scars (RS) diagnosed on core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB), excision by VAB in preference to open surgery, and for atypical ductal hyperplasia (ADH) and phyllodes tumors (PT) diagnosed at VAB or CNB, first-line open surgical excision (OE) with follow-up surveillance imaging for 5 years. Analyzing the Database of the Swiss Minimally Invasive Breast Biopsies (MIBB) with more than 30,000 procedures recorded, there was a significant increase in recommending more frequent surveillance of LN [65% in 2018 vs. 51% in 2016 (p = 0.004)], FEA (72% in 2018 vs. 62% in 2016 (p = 0.005)), and PL [(76% in 2018 vs. 70% in 2016 (p = 0.04)] diagnosed on VAB. A trend to more frequent surveillance was also noted also for RS [77% in 2018 vs. 67% in 2016 (p = 0.07)]. CONCLUSIONS: Minimally invasive management of B3 lesions (except ADH and PT) with VAB continues to be appropriate as an alternative to first-line OE in most cases, but with more frequent surveillance, especially for LN.

Pre-treatment functional MRI of breast cancer: T2* evaluation at 3 T and relationship to dynamic contrast-enhanced and diffusion-weighted imaging.

PURPOSE: Baseline T2* relaxation time has been proposed as an imaging biomarker in cancer, in addition to Dynamic Contrast-Enhanced (DCE) MRI and diffusion-weighted imaging (DWI) parameters. The purpose of the current work is to investigate sources of error in T2* measurements and the relationship between T2* and DCE and DWI functional parameters in breast cancer. METHODS: Five female volunteers and thirty-two women with biopsy proven breast cancer were scanned at 3 T, with Research Ethics Committee approval. T2* values of the normal breast were acquired from high-resolution, low-resolution and fat-suppressed gradient-echo sequences in volunteers, and compared. In breast cancer patients, pre-treatment T2*, DCE MRI and DWI were performed at baseline. Pathologically complete responders at surgery and non-responders were identified and compared. Principal component analysis (PCA) and cluster analysis (CA) were performed. RESULTS: There were no significant differences between T2* values from high-resolution, low-resolution and fat-suppressed datasets (p > 0.05). There were not significant differences between baseline functional parameters in responders and non-responders (p > 0.05). However, there were differences in the relationship between T2* and contrast-agent uptake in responders and non-responders. Voxels of similar characteristics were grouped in 5 clusters, and large intra-tumoural variations of all parameters were demonstrated. CONCLUSION: Breast T2* measurements at 3 T are robust, but spatial resolution should be carefully considered. T2* of breast tumours at baseline is unrelated to DCE and DWI parameters and contribute towards describing functional heterogeneity of breast tumours.

Quantitative evaluation of contrast agent uptake in standard fat-suppressed dynamic contrast-enhanced MRI examinations of the breast.

PURPOSE: To propose a method to quantify T1 and contrast agent uptake in breast dynamic contrast-enhanced (DCE) examinations undertaken with standard clinical fat-suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas. METHODS: A standard fat-suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)-weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B0 field inhomogeneity was assessed in test objects and healthy volunteers. The T1 of breast tumors was calculated at different time points (pre-, peak-, and post-contrast agent administration) for 20 patients, pre-treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank-sum test). RESULTS: The calibration curves proved to be highly reproducible (coefficient of variation under 10%). T1 measurements were affected by B0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat-suppressed T1 measurements of breast parenchyma in volunteers. The values of T1 measured pre-, peak-, and post-contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T1 for that range. Significant differences were identified in the width of the distributions of the post-contrast T1 values between lobular and ductal carcinomas (P < 0.05); lobular carcinomas demonstrated a wider range of post-contrast T1 values, potentially related to their infiltrative growth pattern. CONCLUSIONS: This work has demonstrated the feasibility of fat-suppressed T1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between lobular and invasive ductal carcinomas, and further enables the optimization of DCE protocols by tailoring the dynamic range of the sequence to the values of T1 measured.

Initial experience of the BREAST-Q breast-conserving therapy module.

PURPOSE: The most recently developed module of the BREAST-Q, a validated patient outcome measure, is for patients who have undergone breast-conserving therapy (BCT) for cancer. This aim of this study was to assess patient satisfaction and quality of life after BCT using BREAST-Q, investigate clinical risk factors for lower satisfaction and explore the relationship between patient satisfaction with the appearance of their breasts and the other domains of the BREAST-Q. METHODS: Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate at the time of their annual surveillance mammogram. Clinicopathological data were collected from an electronic database. Linear regression was used to evaluate risk factors for lower satisfaction. Spearman's rho correlation coefficients were calculated to evaluate the relationship between domains. RESULTS: 200 women completed the questionnaire. Mean age was 60 years (SD 11.1). Time from surgery was 35.5 months (SD 17.8). Median score for 'Satisfaction with breasts' was 68 (interquartile range 55-80). Lowest scores were for 'sexual wellbeing' (57, IQR 45-66). On multivariate analysis, BMI at the time of surgery (p = 0.002), delayed wound healing (p = 0.001) and axillary surgery (p = 0.003) were independent risk factors for lower satisfaction. There was significant correlation between 'Satisfaction with breasts' and all other BREAST-Q domains. CONCLUSION: High BMI, delayed wound healing and axillary surgery are risk factors for lower patient satisfaction. This first publication reporting the whole dataset for the BREAST-Q BCT will serve as a benchmark for future studies of patient satisfaction following BCT.

First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

The purpose of this study is to obtain a consensus for the therapy of B3 lesions. The first International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumors (PT), and radial scars (RS) took place in January 2016 in Zurich, Switzerland organized by the International Breast Ultrasound School and the Swiss Minimally Invasive Breast Biopsy group-a subgroup of the Swiss Society of Senology. Consensus recommendations for the management and follow-up surveillance of these B3 lesions were developed and areas of research priorities were identified. The consensus recommendation for FEA, LN, PL, and RS diagnosed on core needle biopsy or vacuum-assisted biopsy (VAB) is to therapeutically excise the lesion seen on imaging by VAB and no longer by open surgery, with follow-up surveillance imaging for 5 years. The consensus recommendation for ADH and PT is, with some exceptions, therapeutic first-line open surgical excision. Minimally invasive management of selected B3 lesions with therapeutic VAB is acceptable as an alternative to first-line surgical excision.

Multi-parametric MRI in the early prediction of response to neo-adjuvant chemotherapy in breast cancer: Value of non-modelled parameters.

OBJECTIVE: To prospectively evaluate individual functional MRI metrics for the early prediction of pathological complete response (pCR) to neo-adjuvant chemotherapy (NAC) in breast cancer. MATERIALS AND METHODS: Thirty-two women (median age 52 years; range 32-71 years) with biopsy proven breast cancer due to receive neo-adjuvant anthracycline and/or taxane-based chemotherapy were prospectively recruited following local research ethics committee approval and written informed consent. Breast MRI was performed prior to and after two cycles of NAC and pCR was assessed after surgery. The enhancement fraction (EF), tumour volume, initial area under the gadolinium curve (IAUGC), pharmacokinetic parameters (K(trans), kep and ve), the apparent diffusion coefficient (ADC) and R2* values, along with the percentage change in these parameters after two cycles were evaluated according to pCR status using an independent samples t-test. The area under the receiver operating characteristics curve (AUC) was calculated for each parameter. Linear discriminant analysis (LDA) determined the most important parameter in predicting pCR. RESULTS: A reduction in the EF (-41% ± 38%) and tumour volume (-80% ± 25%) after 2 cycles of NAC were significantly greater in those achieving pCR (p=0.025, p=0.011 respectively). A reduction in the EF of 7% after 2 cycles of NAC identified those more likely to achieve pCR (AUC 0.76). AUC changes in other parameters were tumour volume (0.77), IAUGC (0.64), K(trans) (0.60), kep (0.68), ve (0.58), ADC (0.69) and R2* (0.41). CONCLUSION: In a multi-parametric MRI model, the decrease in a non-model based vascular parameter the enhancement fraction as well as the tumour volume are the most important early predictors of pCR in breast cancer.

Evaluating the diagnostic sensitivity of computed diffusion-weighted MR imaging in the detection of breast cancer.

PURPOSE: To evaluate the diagnostic sensitivity of computed diffusion-weighted (DW)-MR imaging for the detection of breast cancer. MATERIALS AND METHODS: Local research ethics approval was obtained. A total of 61 women (median 48 years) underwent dynamic contrast enhanced (DCE)- and DW-MR between January 2011 and March 2012, including 27 with breast cancer on core biopsy and 34 normal cases. Standard ADC maps using all four b values (0, 350, 700, 1150) were used to generate computed DW-MR images at b = 1500 s/mm(2) and b = 2000 s/mm(2) . Four image sets were read sequentially by two readers: acquired b = 1150 s/mm(2) , computed b = 1500 s/mm(2) and b = 2000 s/mm(2) , and DCE-MR at an early time point. Cancer detection was rated using a five-point scale; image quality and background suppression were rated using a four-point scale. The diagnostic sensitivity for breast cancer detection was compared using the McNemar test and inter-reader agreement with a Kappa value. RESULTS: Computed DW-MR resulted in higher overall diagnostic sensitivity with b = 2000 s/mm(2) having a mean diagnostic sensitivity of 76% (range 49.8-93.7%) and b = 1500 s/mm(2) having a mean diagnostic sensitivity of 70.3% (range 32-97.7%) compared with 44.4% (range 25.5-64.7%) for acquired b = 1150 s/mm(2) (both p = 0.0001). Computed DW-MR images produced better image quality and background suppression (mean scores for both readers: 2.55 and 2.9 for b 1500 s/mm(2) ; 2.55 and 3.15 for b 2000 s/mm(2) , respectively) than the acquired b value 1150 s/mm(2) images (mean scores for both readers: 2.4 and 2.45, respectively). CONCLUSION: Computed DW-MR imaging has the potential to improve the diagnostic sensitivity of breast cancer detection compared to acquired DW-MR. J. Magn. Reson. Imaging 2016;44:130-137.

Evaluation of diffusion models in breast cancer.

PURPOSE: The purpose of this study is to investigate whether the microvascular pseudodiffusion effects resulting with non-monoexponential behavior are present in breast cancer, taking into account tumor spatial heterogeneity. Additionally, methodological factors affecting the signal in low and high diffusion-sensitizing gradient ranges were explored in phantom studies. METHODS: The effect of eddy currents and accuracy of b-value determination using a multiple b-value diffusion-weighted MR imaging sequence were investigated in test objects. Diffusion model selection and noise were then investigated in volunteers (n = 5) and breast tumor patients (n = 21) using the Bayesian information criterion. RESULTS: 54.3% of lesion voxels were best fitted by a monoexponential, 26.2% by a stretched-exponential, and 19.5% by a biexponential intravoxel incoherent motion (IVIM) model. High correlation (0.92) was observed between diffusion coefficients calculated using mono- and stretched-exponential models and moderate (0.59) between monoexponential and IVIM (medians: 0.96/0.84/0.72 × 10(-3) mm(2)/s, respectively). Distortion due to eddy currents depended on the direction of the diffusion gradient and displacement varied between 1 and 6 mm for high b-value images. Shift in the apparent diffusion coefficient due to intrinsic field gradients was compensated for by averaging diffusion data obtained from opposite directions. CONCLUSIONS: Pseudodiffusion and intravoxel heterogeneity effects were not observed in approximately half of breast cancer and normal tissue voxels. This result indicates that stretched and IVIM models should be utilized in regional analysis rather than global tumor assessment. Cross terms between diffusion-sensitization gradients and other imaging or susceptibility-related gradients are relevant in clinical protocols, supporting the use of geometric averaging of diffusion-weighted images acquired with diffusion-sensitization gradients in opposite directions.

Alternative screening for dense breasts: MRI.

OBJECTIVE. The purpose of this article is to review the use of MRI in breast density measurement and breast cancer risk estimation and to discuss the role of MRI as an alternative screening to mammography for screening women with dense breasts. CONCLUSION. The potential of MRI for screening women with dense breasts remains controversial because of the paucity of clinical evidence, the possibility of overdiagnosis, and the cost-effectiveness of the technique in this population. Although methods of MRI measurement require standardization and automation, future addition of MRI density to risk models may positively impact their value.

Diffusion-weighted imaging of the high-risk breast: Apparent diffusion coefficient values and their relationship to breast density.

PURPOSE: To document the apparent diffusion coefficient (ADC) of fibroglandular breast tissue in women at high-risk of developing breast cancer and investigate the relationship between ADC and breast density. MATERIALS AND METHODS: Local research ethics approval was obtained. A total of 33 high-risk women including 17 BRCA1/2 mutation carriers (mean age, 43 years) and 16 women postmantle irradiation (mean age 40 years) underwent diffusion-weighted MRI between days 6 and 16 of their menstrual cycle. ADC histograms from a region of interest in fibroglandular tissue and mammographic breast density measurements were obtained. Mean, percentile ADC values (10th, 25th, 50th, 75th, 90th) and skew were compared for the two groups; ADC and mammographic breast density were correlated. RESULTS: Mean ADC values (×10(-6) mm(2) /s) were 2017 ± 197 in postmantle irradiated women and 1827 ± 289 in BRCA1/2 mutation carriers (P = 0.035) with significant differences at all percentiles (P < 0.0001) but not skew (P = 0.44). ADC values showed weak positive correlation with mammographic breast density in BRCA1/2 mutation carriers (r = 0.51, P = 0.043) but not in postmantle radiotherapy patients (r = 0.49, P = 0.13). CONCLUSION: Higher ADC values seen in fibroglandular tissue postmantle irradiation compared with BRCA1/2 mutation carriers has potential to improve tumor detection in these patients. Lack of correlation between ADC and breast density postmantle irradiation may be a result of microstructural changes.

Functional imaging biomarkers for assessing response to treatment in liver and lung metastases.

Management of patients with metastatic cancer and development of new treatments rely on imaging to provide non-invasive biomarkers of tumour response and progression. The widely used size-based criteria have increasingly become inadequate where early measures of response are required to avoid toxicity of ineffective treatments, as biological, physiologic, and molecular modifications in tumours occur before changes in gross tumour size. A multiparametric approach with the current range of imaging techniques allows functional aspects of tumours to be simultaneously interrogated. Appropriate use of these imaging techniques and their timing in relation to the treatment schedule, particularly in the context of clinical trials, is fundamental. There is a lack of consensus regarding which imaging parameters are most informative for a particular disease site and the best time to image so that, despite an increasing body of literature, open questions on these aspects remain. In addition, standardization of these new parameters is required. This review summarizes the published literature over the last decade on functional and molecular imaging techniques in assessing treatment response in liver and lung metastases.

Deformation-compensated averaging for clutter reduction in epiphotoacoustic imaging in vivo.

Photoacoustic imaging, based on ultrasound detected after laser irradiation, is an extension to diagnostic ultrasound for imaging the vasculature, blood oxygenation and the uptake of optical contrast media with promise for cancer diagnosis. For versatile scanning, the irradiation optics is preferably combined with the acoustic probe in an epi-style arrangement avoiding acoustically dense tissue in the acoustic propagation path from tissue irradiation to acoustic detection. Unfortunately epiphotoacoustic imaging suffers from strong clutter, arising from optical absorption in tissue outside the image plane, and from acoustic backscattering. This limits the imaging depth for useful photoacoustic image contrast to typically less than one centimeter. Deformation-compensated averaging (DCA), which takes advantage of clutter decorrelation induced by palpating the tissue with the imaging probe, has previously been proposed for clutter reduction. We demonstrate for the first time that DCA results in reduced clutter in real-time freehand clinical epiphotoacoustic imaging. For this purpose, combined photoacoustic and pulse-echo imaging at 10-Hz frame rate was implemented on a commercial scanner, allowing for ultrasound-based motion tracking inherently coregistered with photoacoustic frames. Results from the forearm and the neck confirm that contrast is improved and imaging depth increased by DCA.

Diffusion weighted imaging of the normal breast: reproducibility of apparent diffusion coefficient measurements and variation with menstrual cycle and menopausal status.

OBJECTIVES: To establish the reproducibility of apparent diffusion coefficient (ADC) measurements in normal fibroglandular breast tissue and to assess variation in ADC values with phase of the menstrual cycle and menopausal status. METHODS: Thirty-one volunteers (13 premenopausal, 18 postmenopausal) underwent magnetic resonance twice (interval 11-22 days) using diffusion-weighted MRI. ADC(total) and a perfusion-insensitive ADC(high) (omitting b = 0) were calculated. Reproducibility and inter-observer variability of mean ADC values were assessed. The difference in mean ADC values between the two phases of the menstrual cycle and the postmenopausal breast were evaluated. RESULTS: ADC(total) and ADC(high) showed good reproducibility (r% = 17.6, 22.4). ADC(high) showed very good inter-observer agreement (kappa = 0.83). The intraclass correlation coefficients (ICC) were 0.93 and 0.91. Mean ADC values were significantly lower in the postmenopausal breast (ADC(total) 1.46 ± 0.3 × 10(-3) mm(2)/s, ADC(high) 1.33 ± 0.3 × 10(-3) mm(2)/s) compared with the premenopausal breast (ADC(total) 1.84 ± 0.26 × 10(-3) mm(2)/s, ADC(high) 1.77 ± 0.26 × 10(-3) mm(2)/s; both P < 0.001). No significant difference was seen in ADC values in relation to menstrual cycle (ADC(total) P = 0.2, ADC(high) P = 0.24) or between postmenopausal women taking or not taking oestrogen supplements (ADC(total) P = 0.6, ADC(high) P = 0.46). CONCLUSIONS: ADC values in fibroglandular breast tissue are reproducible. Lower ADC values within the postmenopausal breast may reduce diffusion-weighted contrast and have implications for accurately detecting tumours. KEY POINTS: • ADC values from fibroglandular breast tissue are measured reproducibly by multiple observers. • Mean ADC values were significantly lower in postmenopausal than premenopausal breast tissue. • Mean ADC values did not vary significantly with menstrual cycle. • Low postmenopausal ADC values may hinder tumour detection on DW-MRI.