Lindsay W. Turnbull

Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial

BACKGROUND MRI might improve diagnosis of breast cancer, reducing rates of reoperation. We assessed the clinical efficacy of contrast-enhanced MRI in women with primary breast cancer. METHODS We undertook an open, parallel group trial in 45 UK centres, with 1623 women aged 18 years or older with biopsy-proven primary breast cancer who were scheduled for wide local excision after triple assessment. Patients were randomly assigned to receive either MRI (n=816) or no further imaging (807), with use of a minimisation algorithm incorporating a random element. The primary endpoint was the proportion of patients undergoing a repeat operation or further mastectomy within 6 months of random assignment, or a pathologically avoidable mastectomy at initial operation. Analysis was by intention to treat. This study is registered, ISRCTN number 57474502. FINDINGS 816 patients were randomly assigned to MRI and 807 to no MRI. Addition of MRI to conventional triple assessment was not significantly associated with reduced a reoperation rate, with 153 (19%) needing reoperation in the MRI group versus 156 (19%) in the no MRI group, (odds ratio 0.96, 95% CI 0.75-1.24; p=0.77). INTERPRETATION Our findings are of benefit to the NHS because they show that MRI might be unnecessary in this population of patients to reduce repeat operation rates, and could assist in improved use of NHS services. FUNDING National Institute for Health Researchs Health Technology Assessment Programme.

Correlation of ADC and T2 Measurements With Cell Density in Prostate Cancer at 3.0 Tesla

Objectives:To assess the relationship between MRI derived parameters (apparent diffusion coefficient (ADC) and T2 relaxation time) and tumor cellularity as determined from whole mounted radical prostatectomy specimens, for both prostatic carcinoma and normal peripheral zone tissue. Materials and Methods:Over a 16-month period, 20 patients (mean age: 61 years, range: 42–70 years) were prospectively recruited. Diffusion and T2 imaging were performed on a 3.0 Tesla scanner to enable subsequent ADC and T2 calculation. After radical retropubic prostatectomy specimens were whole-mounted and regions of interest (ROIs) drawn in areas of prostatic carcinoma and normal peripheral zone. Cell density was then determined using an adaptive histogram thresholding technique. Differences in tissue type were explored using the unpaired t test while the relationship between parameters was assessed using scatter-plots and the Pearson correlation coefficient. Results:Significant differences (P < 0.0001 in all cases) were noted between peripheral zone tissue and prostatic carcinoma in terms of ADC (1.88 ± 0.22 vs. 1.43 ± 0.19 × 10−3 mm2/s), T2 (142 ± 24 vs. 109 ± 20 milliseconds), and cell density (9.4% ± 3.0% vs. 19.8% ± 5.3%). A significant negative correlation with cell density was noted for both ADC (R = −0.695, P < 0.0001) and T2 (R = −0.505, P = 0.001). Trends for increased cell density, decreased ADC, and decreased T2 with increasing Gleason score were also noted. Conclusions:ADC and to a lesser extent T2 are good indicators of cell density. Because of the potential link with Gleason score, MRI derived parameters may have a prognostic role with regard to potential metastatic activity and tumor aggressiveness.

Correlation of diffusion-weighted magnetic resonance data with cellularity in prostate cancer

To assess the relationship between the apparent diffusion coefficient (ADC) on magnetic resonance imaging (MRI) and cell density (CD) obtained from radical prostatectomy (RP) specimens.

Comparison of quantitative T2 mapping and diffusion-weighted imaging in the normal and pathologic prostate.

In this study, diffusion‐weighted images of the human prostate were successfully obtained, enabling quantification of apparent diffusion coefficients (ADCs) in normal and pathologic regions. A dual acquisition fast spin‐echo sequence was used for accurate T2 calculation. T2 values were significantly higher in the peripheral zone than the central gland (P = 0.015). No significant correlations were found in either normal or pathologic tissue between ADC values and relaxation rates for all three gradient directions and the orientationally averaged water diffusion coefficient. Evidence suggesting that diffusional anisotropy is present in normal prostatic tissue is also detailed, with significant differences noted between the z‐component and both the x‐ and y‐components of the ADC for peripheral zone (P < 0.040) and central gland (P < 0.001). Magn Reson Med 46:1054–1058, 2001.

Role of dynamic contrast enhanced MRI in monitoring early response of locally advanced breast cancer to neoadjuvant chemotherapy

Neoadjuvant chemotherapy has become the standard treatment for patients with locally advanced breast cancer; however a technique that can accurately differentiate responders from non-responders at an early time point during treatment has still to be identified. The purpose of this work was to evaluate the ability of pharmacokinetically modelled dynamic contrast-enhanced MRI data to predict and monitor response of patients diagnosed with locally advanced breast cancer to neoadjuvant chemotherapy, at an early time point during treatment. Sixty-eight patients with histology proven breast cancer underwent MRI examination prior to treatment, early during treatment and following the final cycle of chemotherapy. A two compartment pharmacokinetic model provided the kinetic parameters transfer constant (Ktrans), rate constant (Kep) and extracellular extravascular space (Ve) for a region of interest encompassing the whole lesion (ROIwhole) and a 3 × 3 pixel ‘hot-spot’ showing the greatest mean maximum percentage enhancement from within that region (ROIhs). Following treatment 48 patients were classified as responders and 20 as non-responders based on total tumour volume reduction. Tumour volume changes between the pre-treatment and early treatment time points demonstrated differences between responders and non-responders with percentage change revealing the most significant result (p < 0.001). Analysis based on ROIhsprovided more statistically significant differences between responders and non-responders then ROIwhole analysis. ROIhs analysis demonstrated differences between responders and non-responders both prior to and early during treatment. A highly significant reduction in both Ktrans and Kep (p < 0.001) was noted for responders between the pre-treatment and early treatment time points, while Ve significantly increased during the same time period for non-responders (p < 0.001). Quantification of dynamic contrast enhancement parameters provides a potential means for differentiating responders from non-responders early during their treatment, thereby allowing a prompt change in treatment if necessary.

Textural analysis of contrast-enhanced MR images of the breast

Texture analysis was applied to high‐resolution, contrast‐enhanced (CE) images of the breast to provide a method of lesion discrimination. Significant differences were seen between benign and malignant lesions for a number of textural features, including entropy and sum entropy. Using logistic regression analysis (LRA), a diagnostic accuracy of Az = 0.80 ± 0.07 was obtained with a model requiring only three parameters. By initially dividing the patient data into training and test datasets, reasonable model robustness was also established. On combining features obtained using textural analysis with lesion size, time to maximum enhancement, and patient age, a diagnostic accuracy of Az = 0.92 ± 0.05 was demonstrated. Magn Reson Med 50:92–98, 2003.

Diffusion-weighted imaging of normal and malignant prostate tissue at 3.0T.

To measure the apparent diffusion coefficient (ADC) of normal and malignant prostate tissue at 3.0T using a phased‐array coil and parallel imaging, and determine the utility of ADC values in differentiating tumor from normal peripheral zone (PZ).

Diffusion imaging of the prostate at 3.0 tesla.

Objectives:We sought to assess the efficacy of diffusion imaging in the differential diagnosis of prostatic carcinoma using a 3.0 T scanner and parallel imaging technology. Materials and Methods:Diffusion-weighted images were acquired using a single shot echo-planar imaging sequence with b = 0 and 500 seconds/mm2. Apparent diffusion coefficient (ADCy) values were calculated in tumor and healthy-appearing peripheral zone for 62 patients. Diffusion tensor images were also acquired in 25 patients and mean diffusivity and fractional anisotropy determined. Results:Significant differences were noted between prostatic carcinoma (1.33 ± 0.32 × 10−3 mm2/s) and peripheral zone (1.86 ± 0.47 × 10−3 mm2/s) for ADCy. Significant differences between the 2 tissue types were also noted for mean diffusivity and fractional anisotropy. Utilizing a cut-off of 1.45 × 10−3 mm2/s for mean diffusivity, a sensitivity of 84% and a specificity of 80% were obtained. Conclusions:Diffusion imaging of the prostate was implemented at high magnetic field strength. Reduced ADC and increased fractional anisotropy values were noted in prostatic carcinoma.

Dynamic contrast‐enhanced MRI in the diagnosis and management of breast cancer

Dynamic contrast‐enhanced MRI (DCE‐MRI) is an evolving tool for determining breast disease, which benefits from the move to imaging at 3 T. It has major capabilities for the diagnosis, detection and monitoring of malignancy. It benefits from being non‐invasive and three‐dimensional, allowing visualisation of the extent of disease and its angiogenic properties, visualisation of lesion heterogeneity, detection of changes in angiogenic properties before morphological alterations, and the potential to predict the overall response either before the start of therapy or early during treatment. In addition, DCE‐MRI is emerging as a powerful tool for screening high‐risk patients and for detecting high‐grade ductal carcinoma in situ. However, there are also a number of limitations, including the overlap in enhancement patterns between malignant and benign disease, the failure to resolve microscopic disease particularly in the neoadjuvant setting, and the inconsistent predictive value of the enhancement pattern for clinical outcome. Careful consideration should be given to the technical requirements of individual examinations and the need for automation of post‐processing techniques to appropriately handle the growing volume of data acquired. Research continues, focusing on the use of higher field strengths with improved spatial and temporal resolution data, improving understanding of the mechanism of contrast enhancement at the cellular level, and developing macromolecular and targeted contrast agents. Copyright

Magnetic resonance imaging screening in women at genetic risk of breast cancer: imaging and analysis protocol for the UK multicentre study

The imaging and analysis protocol of the UK multicentre study of magnetic resonance imaging (MRI) as a method of screening for breast cancer in women at genetic risk is described. The study will compare the sensitivity and specificity of contrast-enhanced MRI with two-view x-ray mammography. Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for three years, with annual MRI and x-ray mammography continuing for up to 5 years. A symptomatic cohort will be measured in the first year to ensure consistent reporting between centres. The MRI examination comprises a high-sensitivity three-dimensional contrast-enhanced assessment, followed by a high-specificity contrast-enhanced study in equivocal cases. Multiparametric analysis will encompass morphological assessment, the kinetics of contrast agent uptake and determination of quantitative pharmacokinetic parameters. Retrospective analysis will identify the most specific indicators of malignancy. Sensitivity and specificity, together with diagnostic performance, diagnostic impact and therapeutic impact will be assessed with reference to pathology, follow-up and changes in diagnostic certainty and therapeutic decisions. Mammography, lesion localisation, pathology and cytology will be performed in accordance with the UK NHS Breast Screening Programme quality assurance standards. Similar standards of quality assurance will be applied for MR measurements and evaluation.