Monique D. Dorrius

Diffusion-weighted imaging of normal fibroglandular breast tissue: influence of microperfusion and fat suppression technique on the apparent diffusion coefficient.

The influence of microperfusion and fat suppression technique on the apparent diffusion coefficient (ADC) values obtained with diffusion weighted imaging (DWI) of normal fibroglandular breast tissue was investigated. Seven volunteers (14 breasts) were scanned using diffusion weighting factors (b values) up to 1600 s/mm2 and the four different fat suppression techniques: STIR, fat saturation, SPAIR, and Water Excitation. The relationship between the logarithmic DW attenuation curves and b was linear for b values up to 600 s/mm2 (R2 > 0.999). Small differences were noted between the ADC values obtained with the various fat suppression methods, especially at the higher b values. Water Excitation had the highest mean SNR, exceeding STIR (p = 0.03) though not significantly different from fat saturation and SPAIR. In conclusion, the ADC of fibroglandular breast tissue is not influenced by microperfusion and Water Excitation is recommended because it yielded the best SNR values. These factors may be crucial in the differentiation between benign and malignant lesions. Copyright

Computer-aided detection in breast MRI: a systematic review and meta-analysis

ObjectivesTo evaluate the additional value of computer-aided detection (CAD) in breast MRI by assessing radiologists’ accuracy in discriminating benign from malignant breast lesions.MethodsA literature search was performed with inclusion of relevant studies using a commercially available CAD system with automatic colour mapping. Two independent researchers assessed the quality of the studies. The accuracy of the radiologists’ performance with and without CAD was presented as pooled sensitivity and specificity.ResultsOf 587 articles, 10 met the inclusion criteria, all of good methodological quality. Experienced radiologists reached comparable pooled sensitivity and specificity before and after using CAD (sensitivity: without CAD: 89%; 95% CI: 78–94%, with CAD: 89%; 95%CI: 81–94%) (specificity: without CAD: 86%; 95% CI: 79–91%, with CAD: 82%; 95% CI: 76–87%). For residents the pooled sensitivity increased from 72% (95% CI: 62–81%) without CAD to 89% (95% CI: 80–94%) with CAD, however, not significantly. Concerning specificity, the results were similar (without CAD: 79%; 95% CI: 69–86%, with CAD: 78%; 95% CI: 69–84%).ConclusionsCAD in breast MRI has little influence on the sensitivity and specificity of experienced radiologists and therefore their interpretation remains essential. However, residents or inexperienced radiologists seem to benefit from CAD concerning breast MRI evaluation.

The dream of a one-stop-shop: Meta-analysis on myocardial perfusion CT

PURPOSE To determine the diagnostic performance of computed tomography (CT) perfusion techniques for the detection of functionally relevant coronary artery disease (CAD) in comparison to reference standards, including invasive coronary angiography (ICA), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). MATERIALS AND METHODS PubMed, Web of Knowledge and Embase were searched from January 1, 1998 until July 1, 2014. The search yielded 9475 articles. After duplicate removal, 6041 were screened on title and abstract. The resulting 276 articles were independently analyzed in full-text by two reviewers, and included if the inclusion criteria were met. The articles reporting diagnostic parameters including true positive, true negative, false positive and false negative were subsequently evaluated for the meta-analysis. Results were pooled according to CT perfusion technique, namely snapshot techniques: single-phase rest, single-phase stress, single-phase dual-energy stress and combined coronary CT angiography [rest] and single-phase stress, as well the dynamic technique: dynamic stress CT perfusion. RESULTS Twenty-two articles were included in the meta-analysis (1507 subjects). Pooled per-patient sensitivity and specificity of single-phase rest CT compared to rest SPECT were 89% (95% confidence interval [CI], 82-94%) and 88% (95% CI, 78-94%), respectively. Vessel-based sensitivity and specificity of single-phase stress CT compared to ICA-based >70% stenosis were 82% (95% CI, 64-92%) and 78% (95% CI, 61-89%). Segment-based sensitivity and specificity of single-phase dual-energy stress CT in comparison to stress MRI were 75% (95% CI, 60-85%) and 95% (95% CI, 80-99%). Segment-based sensitivity and specificity of dynamic stress CT perfusion compared to stress SPECT were 77% (95% CI, 67-85) and 89% (95% CI, 78-95%). For combined coronary CT angiography and single-phase stress CT, vessel-based sensitivity and specificity in comparison to ICA-based >50% stenosis were 84% (95% CI, 67-93%) and 93% (95% CI, 89-96%). CONCLUSION This meta-analysis shows considerable variation in techniques and reference standards for CT of myocardial blood supply. While CT seems sensitive and specific for evaluation of hemodynamically relevant CAD, studies so far are limited in size. Standardization of myocardial perfusion CT technique is essential.

Role of baseline nodule density and changes in density and nodule features in the discrimination between benign and malignant solid indeterminate pulmonary nodules

PURPOSE To retrospectively evaluate whether baseline nodule density or changes in density or nodule features could be used to discriminate between benign and malignant solid indeterminate nodules. MATERIALS AND METHODS Solid indeterminate nodules between 50 and 500 mm(3) (4.6-9.8mm) were assessed at 3 and 12 months after baseline lung cancer screening (NELSON study). Nodules were classified based on morphology (spherical or non-spherical), shape (round, polygonal or irregular) and margin (smooth, lobulated, spiculated or irregular). The mean CT density of the nodule was automatically generated in Hounsfield units (HU) by the Lungcare software. RESULTS From April 2004 to July 2006, 7310 participants underwent baseline screening. In 312 participants 372 solid purely intra-parenchymal nodules were found. Of them, 16 (4%) were malignant. Benign nodules were 82.8mm(3) (5.4mm) and malignant nodules 274.5mm(3) (8.1mm) (p=0.000). Baseline CT density for benign nodules was 42.7 HU and for malignant nodules -2.2 HU (p=ns). The median change in density for benign nodules was -0.1 HU and for malignant nodules 12.8 HU (p<0.05). Compared to benign nodules, malignant nodules were more often non-spherical, irregular, lobulated or spiculated at baseline, 3-month and 1-year follow-up (p<0.0001). In the majority of the benign and malignant nodules there was no change in morphology, shape and margin during 1 year of follow-up (p=ns). CONCLUSION Baseline nodule density and changes in nodule features cannot be used to discriminate between benign and malignant solid indeterminate pulmonary nodules, but an increase in density is suggestive for malignancy and requires a shorter follow-up or a biopsy.

Determination of Choline Concentration in Breast Lesions: Quantitative Multivoxel Proton MR Spectroscopy as a Promising Noninvasive Assessment Tool to Exclude Benign Lesions

PURPOSE To determine the optimal cutoff of choline (Cho) concentration in quantitative multivoxel magnetic resonance (MR) spectroscopic data to safely prove benignancy in breast lesions. MATERIALS AND METHODS The study was institutional review board approved, and informed consent was obtained from each patient. Between July 2009 and July 2010, multivoxel MR spectroscopy was performed in 24 consecutive patients with 25 breast lesions assessed as Breast Imaging Reporting and Data System 3 or 4 and larger than 1 cm in diameter at mammography. Two-dimensional point-resolved spatially localized spectroscopy chemical shift imaging was first performed without signal suppression (repetition time msec/echo time msec, 1500/30) as reference measurement and was performed subsequently with suppression of water and fat signals (1500/135) to detect Cho. Differences in mean and highest Cho concentration in the breast lesions were tested for significance by using the independent sample t test. The final diagnosis was confirmed with pathologic findings. RESULTS Fourteen of 25 breast lesions were malignant. The mean Cho concentration varied between 0.3 and 1.3 mmol/L (0.84 mmol/L ± 0.32 [standard deviation]) in benign lesions and between 1.3 and 9.5 mmol/L (3.10 mmol/L ± 2.21) in malignant lesions. The highest Cho concentrations in benign and malignant lesions were 0.4-1.5 mmol/L (1.19 mmol/L ± 0.33) and 1.7-11.8 mmol/L (4.08 mmol/L ± 2.81), respectively. Mean and highest Cho concentrations in benign and malignant breast lesions differed significantly (P = .02 for both). CONCLUSION The study, in a relatively small patient population, shows that quantitative multivoxel MR spectroscopy can be applied to exclude benign breast lesions from further invasive diagnostic work-up with the implementation of a Cho concentration of 1.5 mmol/L or lower as a cutoff. Further larger studies will be needed to confirm these results.

The negative predictive value of breast Magnetic Resonance Imaging in noncalcified BIRADS 3 lesions

PURPOSE The purpose of this study is to determine whether breast MRI can provide a sufficient NPV to safely rule out malignancy in mammographic BIRADS 3 lesions. MATERIALS AND METHODS In a 3-year consecutive mammographic examination study 176 out of 4391 patients had a lesion classified as BIRADS 3. 76 out of 176 patients underwent breast MRI as diagnostic work-up. Lesions which MRI classified as BIRADS 1 or 2 were considered negative for malignancy. Sensitivity, specificity, PPV and NPV were calculated. RESULTS In 27 out of 76 (35.5%) patients MRI showed no enhancement and was classified as BIRADS 1. In 25 (32.9%) patients MRI showed focal or mass enhancement classified as BIRADS 2. In these 52 (68.4%) patients no malignancy was found during at least 2 years study follow-up. The other 24 (31.6%) patients had a lesion classified as BIRADS ≥ 3. Thirteen of these 24 lesions were malignant by pathology. MRI had a sensitivity of 100% (95% CI: 75-100%), specificity of 82.5% (95% CI: 71-91%), PPV of 54.2% (95% CI: 33-74%) and NPV of 100% (95% CI: 93-100%). CONCLUSION Breast MRI should be used in a diagnostic strategy for the work-up of noncalcified BIRADS 3 lesions. Malignancy is ruled out with a very high level of confidence in the majority of patients (68%), herewith avoiding invasive diagnostic procedures.

Quantitative multivoxel proton chemical shift imaging of the breast

The study of focal pathology by single-voxel magnetic resonance spectroscopy (MRS) is hampered by the impossibility to study tissue heterogeneity or compare the metabolite signals in breast lesion directly to those in unaffected tissue. Multivoxel MRS studies, while potentially allowing for truly quantitative tissue characterization, have up to now also been far from quantitative with, for example, the signal-to-noise ratio of the choline (Cho) signal serving as measure of tumor activity. Shown in this study is that in a standard clinical setting with a regular 1.5-T magnetic resonance scanner, it is possible to perform quantitative multivoxel MRS. With the use of literature values for the T1 and T2 relaxation times of Cho and water in fibroglandular breast tissue and tumors, one can determine the concentrations of Cho in different tumor compartments and surrounding tissues in two brief multivoxel MRS measurements. This opens excellent perspectives to quantitative diagnostic and follow-up studies of focal pathology such as lesions suspected of breast cancer.

Comparison of three software systems for semi-automatic volumetry of pulmonary nodules on baseline and follow-up CT examinations

Background Early diagnosis of lung cancer in a treatable stage is the main purpose of lung cancer screening by computed tomography (CT). Accurate three-dimensional size and growth measurements are essential to assess the risk of malignancy. Nodule volumes can be calculated by using semi-automated volumetric software. Systematic differences in volume measurements between packages could influence nodule categorization and management decisions. Purpose To compare volumetric measurements of solid pulmonary nodules on baseline and follow-up CT scans as well as the volume doubling time (VDT) for three software packages. Material and Methods From a Lung Cancer Screening study (NELSON), 50 participants were randomly selected from the baseline round. The study population comprised participants with at least one pulmonary nodule at the baseline and consecutive CT examination. The volume of each nodule was determined for both time points using three semi-automated software packages (P1, P2, and P3). Manual modification was performed when automated assessment was visually inaccurate. VDT was calculated to evaluate nodule growth. Volume, VDT, and nodule management were compared for the three software packages, using P1 as the reference standard. Results In 25 participants, 147 nodules were present on both examinations (volume: 12.0–436.6 mm3). Initial segmentation at baseline was evaluated to be satisfactory in 93.9% of nodules for P1, 84.4 % for P2, and 88.4% for P3. Significant difference was found in measured volume between P1 and the other two packages (P < 0.001). P2 overestimated the volume by 38 ± 24%, and P3 by 50 ± 22%. At baseline, there was consensus on nodule size categorization in 80% for P1&P2 and 74% for P1&P3. At follow-up, consensus on VDT categorization was present in 47% for P1&P2 and 44% for P1&P3. Conclusion Software packages for lung nodule evaluation yield significant differences in volumetric measurements and VDT. This variation affects the classification of lung nodules, especially in follow-up examinations.

Aggressiveness of 'true' interval invasive ductal carcinomas of the breast in postmenopausal women

There is debate whether interval carcinomas differ from screen-detected tumours biologically. In this study, clinico-pathological parameters and the expression of well-validated biological markers were compared between ‘true’ interval carcinomas and screen-detected/missed carcinomas hypothesising that ‘true’ interval carcinomas show a more aggressive biological behaviour. The study group consisted of 92 consecutive postmenopausal women attending the breast screening programme and presenting with an invasive ductal carcinoma. All screening mammograms were re-reviewed. Sixteen patients had a ‘true’ interval carcinoma. Seven carcinomas were missed at screening, but detected on re-reviewing of the screening mammogram. Radiological characteristics were assessed from diagnostic mammograms. Data on patient- and tumour characteristics and follow-up data were recorded from hospital records. Median follow-up was 61 months. Immunohistochemistry for ER, PR, Her2/neu and p53 was performed on TMA sections. Univariate and multivariate logistic regression analyses were performed. In univariate analysis, ‘true’ interval carcinomas were significantly larger (odd ratios (OR) 7.2, 95% CI 1.8–28.1) and less frequently ER (OR 0.3, 95% CI 0.1–0.9) and PR (OR 0.3, 95% CI 0.1–1.0) positive. In multivariate analysis, ‘true’ interval carcinoma was independently associated with larger tumours (OR 7.0, 95% CI 1.4–36.2). A trend toward ER negativity was found (OR 0.3, 95% CI 0.1–1.1). ‘True’ interval carcinomas showed a trend toward a decreased relapse-free survival (HR 1.7 95% CI 0.9–3.1). Although ‘true’ interval carcinomas were significantly larger than screen-detected/missed interval carcinomas, it remains challenging to observe parameters that determine this difference between ‘true’ interval carcinomas and screen-detected lesions.

Features of Resolving and Nonresolving Indeterminate Pulmonary Nodules at Follow-up CT: The NELSON Study

PURPOSE To retrospectively identify features that allow prediction of the disappearance of solid, indeterminate, intraparenchymal nodules detected at baseline computed tomographic (CT) screening of individuals at high risk for lung cancer. MATERIALS AND METHODS The study was institutional review board approved. Participants gave informed consent. Participants with at least one noncalcified, solid, indeterminate, intraparenchymal nodule (volume range, 50-500 mm(3)) at baseline were included (964 nodules in 750 participants). According to protocol, indeterminate nodules were re-examined at a 3-month follow-up CT examination. Repeat screening was performed at years 2 and 4. A nodule was defined as resolving if it did not appear at a subsequent CT examination. Nodule resolution was regarded as spontaneous, not the effect of treatment. CT features of resolving and nonresolving (stable and malignant) nodules were compared by means of generalized estimating equations analysis. RESULTS At subsequent screening, 10.1% (97 of 964) of the nodules had disappeared, 77.3% (n = 75) of these at the 3-month follow-up CT and 94.8% (n = 92) at the second round of screening. Nonperipheral nodules were more likely to resolve than were peripheral nodules (odds ratio: 3.16; 95% confidence interval: 1.76, 5.70). Compared with smooth nodules, nodules with spiculated margins showed the highest probability of disappearance (odds ratio: 4.36; 95% confidence interval: 2.24, 8.49). CONCLUSION Approximately 10% of solid, intermediate-sized, intraparenchymal pulmonary nodules found at baseline screening for lung cancer resolved during follow-up, three-quarters of which had disappeared at the 3-month follow-up CT examination. Resolving pulmonary nodules share CT features with malignant nodules.