The fertilised chick egg and particularly its chorioallantoic membrane (CAM) have drawn continuing interest in biomedicine and bioengineering fields, especially for research on vascular study, ...cancer, drug screening and development, cell factors, stem cells, etc. This literature review systemically introduces the CAM's structural evolution, functions, vascular features and the circulation system, and cell regulatory factors. It also presents the major and updated applications of the CAM in assays for pharmacokinetics and biodistribution, drug efficacy and toxicology testing/screening in preclinical pharmacological research. The time course of CAM applications for different assays and their advantages and limitations are summarised. Among these applications, two aspects are emphasised: (1) potential utility of the CAM for preclinical studies on vascular-disrupting agents (VDAs), promising for anti-cancer vascular-targeted therapy, and (2) modern imaging technologies, including modalities and their applications for real-time visualisation, monitoring and evaluation of the changes in CAM vasculature as well as the interactions occurring after introducing the tested medical, pharmaceutical and biological agents into the system. The aim of this article is to help those working in the biomedical field to familiarise themselves with the chick embryo CAM as an alternative platform and to utilise it to design and optimise experimental settings for their specific research topics.
Objectives
This study was designed to compare the detection of subtle lesions (calcification clusters or masses) when using the combination of digital breast tomosynthesis (DBT) and synthetic ...mammography (SM) with digital mammography (DM) alone or combined with DBT.
Methods
A set of 166 cases without cancer was acquired on a DBT mammography system. Realistic subtle calcification clusters and masses in the DM images and DBT planes were digitally inserted into 104 of the acquired cases. Three study arms were created: DM alone, DM with DBT and SM with DBT. Five mammographic readers located the centre of any lesion within the images that should be recalled for further investigation and graded their suspiciousness. A JAFROC figure of merit (FoM) and lesion detection fraction (LDF) were calculated for each study arm. The visibility of the lesions in the DBT images was compared with SM and DM images.
Results
For calcification clusters, there were no significant differences (
p
> 0.075) in FoM or LDF. For masses, the FoM and LDF were significantly improved in the arms using DBT compared to DM alone (
p
< 0.001). On average, both calcification clusters and masses were more visible on DBT than on DM and SM images.
Conclusions
This study demonstrated that masses were detected better with DBT than with DM alone and there was no significant difference (
p
= 0.075) in LDF between DM&DBT and SM&DBT for calcifications clusters. Our results support previous studies that it may be acceptable to not acquire digital mammography alongside tomosynthesis for subtle calcification clusters and ill-defined masses.
Key Points
•
The detection of masses was significantly better using DBT than with digital mammography alone.
•
The detection of calcification clusters was not significantly different between digital mammography and synthetic 2D images combined with tomosynthesis.
•
Our results support previous studies that it may be acceptable to not acquire digital mammography alongside tomosynthesis for subtle calcification clusters and ill-defined masses for the imaging technology used.
Height-adjusted total kidney volume (htTKV) measured by imaging defined as Mayo Imaging Class (MIC) is a validated prognostic measure for autosomal dominant polycystic kidney disease (ADPKD) in ...adults to predict and stratify disease progression. However, no stratification tool is currently available in pediatric ADPKD. Because magnetic resonance imaging and computed tomography in children are difficult, we propose a novel 3D ultrasound-based pediatric Leuven Imaging Classification to complement the MIC.
A prospective study cohort of 74 patients with genotyped ADPKD (37 female) was followed longitudinally with ultrasound, including 3D ultrasound, and they underwent in total 247 3D ultrasound assessments, with patients' median age (interquartile range IQR) at diagnosis of 3 (IQR, 0-9) years and at first 3D ultrasound evaluation of 10 (5-14) years. First, data matching was done to the published MIC classification, followed by subsequent optimization of parameters and model type.
PKD1 was confirmed in 70 patients (95%), PKD2 in three (4%), and glucosidase IIα unit only once (1%). Over these 247 evaluations, the median height was 143 (IQR, 122-166) cm and total kidney volume was 236 (IQR, 144-344) ml, leading to an htTKV of 161 (IQR, 117-208) ml/m. Applying the adult Mayo classification in children younger than 15 years strongly underestimated ADPKD severity, even with correction for height. We therefore optimized the model with our pediatric data and eventually validated it with data of young patients from Mayo Clinic and the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease used to establish the MIC.
We proposed a five-level Leuven Imaging Classification ADPKD pediatric model as a novel classification tool on the basis of patients' age and 3D ultrasound-htTKV for reliable discrimination of childhood ADPKD severity.
Purpose:
This work proposes a new method of building 3D breast mass models with different morphological shapes and describes the validation of the realism of their appearance after simulation into 2D ...digital mammograms and breast tomosynthesis images.
Methods:
Twenty‐five contrast enhanced MRI breast lesions were collected and each mass was manually segmented in the three orthogonal views: sagittal, coronal, and transversal. The segmented models were combined, resampled to have isotropic voxel sizes, triangularly meshed, and scaled to different sizes. These masses were referred to as nonspiculated masses and were then used as nuclei onto which spicules were grown with an iterative branching algorithm forming a total of 30 spiculated masses. These 55 mass models were projected into 2D projection images to obtain mammograms after image processing and into tomographic sequences of projection images, which were then reconstructed to form 3D tomosynthesis datasets. The realism of the appearance of these mass models was assessed by five radiologists via receiver operating characteristic (ROC) analysis when compared to 54 real masses. All lesions were also given a breast imaging reporting and data system (BIRADS) score. The data sets of 2D mammography and tomosynthesis were read separately. The Kendall's coefficient of concordance was used for the interrater observer agreement assessment for the BIRADS scores per modality. Further paired analysis, using the Wilcoxon signed rank test, of the BIRADS assessment between 2D and tomosynthesis was separately performed for the real masses and for the simulated masses.
Results:
The area under the ROC curves, averaged over all observers, was 0.54 (95% confidence interval 0.50, 0.66) for the 2D study, and 0.67 (95% confidence interval 0.55, 0.79) for the tomosynthesis study. According to the BIRADS scores, the nonspiculated and the spiculated masses varied in their degrees of malignancy from normal (BIRADS 1) to highly suggestive for malignancy (BIRADS 5) indicating the required variety of shapes and margins of these models. The assessment of the BIRADS scores for all observers indicated good agreement based on Kendall's coefficient for both the 2D and the tomosynthesis evaluations. The paired analysis of the BIRADS scores between 2D and tomosynthesis for each observer revealed consistent behavior for the real and simulated masses.
Conclusions:
A database of 3D mass models, with variety of shapes and margins, was validated for the realism of their appearance for 2D digital mammography and for breast tomosynthesis. This database is suitable for use in future observer performance studies whether in virtual clinical trials or in patient images with simulated lesions.
Purpose
We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and ...clinicopathological features.
Methods
Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor-associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays. Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer-specific survival (BCSS).
Results
We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure- and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR = 1.55;
p
= 0.0172) and BCSS (HR = 2.10;
p
< 0.001).
Conclusions
Clinicopathological features, geographical distribution of sTILs and TAPC are similar between pure and non-pure IMPCs. Despite a high proportion of grade 3 tumors and lymph node involvement, we observed a low rate of distant recurrences and breast cancer-related death in this cohort of stage I-III IMPCs treated with primary surgery. Caution in interpretation of the observed prognostic correlations is required given the very low number of events, warranting validation in other cohorts.
Objectives
To study how radiologists’ perceived ability to interpret digital mammography (DM) images is affected by decreases in image quality.
Methods
One view from 45 DM cases (including 30 ...cancers) was degraded to six levels each of two acquisition-related issues (lower spatial resolution and increased quantum noise) and three post-processing-related issues (lower and higher contrast and increased correlated noise) seen during clinical evaluation of DM systems. The images were shown to fifteen breast screening radiologists from five countries. Aware of lesion location, the radiologists selected the most-degraded mammogram (indexed from 1 (reference) to 7 (most degraded)) they still felt was acceptable for interpretation. The median selected index, per degradation type, was calculated separately for calcification and soft tissue (including normal) cases. Using the two-sided, non-parametric Mann-Whitney test, the median indices for each case and degradation type were compared.
Results
Radiologists were not tolerant to increases (medians: 1.5 (calcifications) and 2 (soft tissue)) or decreases (median: 2, for both types) in contrast, but were more tolerant to correlated noise (median: 3, for both types). Increases in quantum noise were tolerated more for calcifications than for soft tissue cases (medians: 3 vs. 4,
p
= 0.02). Spatial resolution losses were considered less acceptable for calcification detection than for soft tissue cases (medians: 3.5 vs. 5,
p
= 0.001).
Conclusions
Perceived ability of radiologists for image interpretation in DM was affected not only by image acquisition-related issues but also by image post-processing issues, and some of those issues affected calcification cases more than soft tissue cases.
Key Points
• Lower spatial resolution and increased quantum noise affected the radiologists’ perceived ability to interpret calcification cases more than soft tissue lesion or normal cases.
• Post-acquisition image processing-related effects, not only image acquisition-related effects, also impact the perceived ability of radiologists to interpret images and detect lesions.
• In addition to current practices, post-acquisition image processing-related effects need to also be considered during the testing and evaluation of digital mammography systems.
Multigene signatures (MGS) are used to guide adjuvant chemotherapy (aCT) decisions in patients diagnosed with estrogen receptor (ER)-positive HER2-negative early breast cancer. We used results from ...three MGS (Oncotype DX® (ODX), MammaPrint® (MP) or Prosigna®) and assessed the concordance between high or low risk of recurrence and the predicted risk of recurrence based on statistical models. In addition, we looked at the impact of MGS results on final aCT administration during the multidisciplinary meeting (MDM). We retrospectively included 129 patients with ER-positive HER2-negative early breast cancer for which MGS testing was performed after MDM at University Hospitals Leuven between May 2013 and April 2019 in case there was doubt about aCT recommendation. Tumor tissue was analyzed either by ODX (N = 44), MP (N = 28), or Prosigna® (N = 57). Eight statistical models were computed: Magee equations (ME), Memorial Sloan Kettering simplified risk score (MSK-SRS), Breast Cancer Recurrence Score Estimator (BCRSE), OncotypeDXCalculator (ODXC), new Adjuvant! Online (nAOL), Mymammaprint.com (MyMP), PREDICT, and SiNK. Concordance, negative percent agreement, and positive percent agreement were calculated. Of 129 cases, 53% were MGS low and 47% MGS high risk. Concordances of 100.0% were observed between risk results obtained by ODX and ME. For MP, BCRSE demonstrated the best concordance, and for Prosigna® the average of ME. Concordances of <50.0% were observed between risk results obtained by ODX and nAOL, ODX and MyMP, ODX and SiNK, MP and MSK-SRS, MP and nAOL, MP and MyMP, MP and SiNK, and Prosigna® and ODXC. Integration of MGS results during MDM resulted in change of aCT recommendation in 47% of patients and a 15% relative and 9% absolute reduction. In conclusion, statistical models, especially ME and BCRSE, can be useful in selecting ER-positive HER2-negative early breast cancer patients who may need MGS testing resulting in enhanced cost-effectiveness and reduced delay in therapeutic decision-making.
To facilitate the development of new brain metastasis (BM) treatment, an easy-to-use and clinically relevant animal model with imaging platform is needed. Rhabdomyosarcoma BM was induced in WAG/Rij ...rats. Post-implantation surveillance and characterizations were systematically performed with multiparametric MRI including 3D T1 and T2 weighted imaging, diffusion-weighted imaging (DWI), T1 and T2 mapping, and perfusion-weighted imaging (PWI), which were validated by postmortem digital radiography (DR), µCT angiography and histopathology. The translational potential was exemplified by the application of a vascular disrupting agent (VDA). BM was successfully induced in most rats of both genders (18/20). Multiparametric MRI revealed significantly higher T2 value, pre-contrast-enhanced (preCE) T1 value, DWI-derived apparent diffusion coefficient (ADC) and CE ratio, but a lower post-contrast-enhanced (postCE) T1 value in BM lesions than in adjacent brain (
p
< 0.01). PWI showed the dynamic and higher contrast agent uptake in the BM compared with the adjacent brain. DR, µCT and histopathology characterized the BM as hypervascular tumors. After VDA treatment, the BM showed drug-related perfusion changes and partial necrosis as evidenced by anatomical, functional MRI parameters and postmortem findings. The present BM model and imaging modalities represent a feasible and translational platform for developing BM-targeting therapeutics.
ABSTRACT
Breast arterial calcification (BAC) is increasingly recognized as a specific marker of medial calcification. The present retrospective observational cohort study aimed to define the ...prevalence, progression rate, risk factors and clinical implications of BAC in chronic kidney disease (CKD) patients across stages of disease. The presence and extent of BAC were determined on mammograms in 310 females (58.7 ± 10.8 years, Caucasian) with CKD across various stages of disease CKD G2–5D n = 132; transplant (Tx) recipients n = 178. In a subset of 88 patients, repeat mammography was performed, allowing us to calculate the annualized BAC rate. Overall, BAC was observed in 34.7% of the patients. BAC prevalence (P = 0.02) and BAC score (P = 0.05) increased along the progression of CKD. In the overall cohort, patients with BAC were characterized by older age, more cardiovascular disease, more inflammation, higher pulse pressure and borderline higher prevalence of diabetes and were more often treated with a vitamin K antagonist (VKA). The BAC progression rate was significantly lower in Tx patients as compared with CKD G5D. Progressors were characterized by more inflammation, worse kidney function, higher BAC score and higher serum phosphate level (Tx only) at baseline and were more often treated with a VKA. Major adverse cardiovascular event-free survival was significantly worse in Tx patients with BAC. In conclusion, BAC is common among CKD patients, progresses at a slower pace in Tx patients as compared with CKD 5D and associates with dismal cardiovascular outcomes. BAC score, kidney function, serum phosphate at baseline and VKA usage seem to be important determinants of progression.
Graphical Abstract
Graphical Abstract
Screening mammography has been widely used over the last few decades to detect breast cancers at an early stage using low-dose X-ray imaging. Being able to detect breast lesions early is highly ...beneficial for the patients as it makes treatment more successful and increases the chance of recovery. However, lesion detection is prone to false negative and false positive results due to the subtlety or low prevalence of the lesions, which compromises patient safety. It is critical to understand human perception and interpretation of images and use such understanding to develop ways to help increase the accuracy of cancer detection. In this paper, we present a large-scale eye-tracking study where 1,568 eye movement trials of expert breast radiologists, trainee radiologists, and physicists were recorded while assessing a large number of mammogram images. First, we statistically analysed viewers’ gaze behaviour based on their mean fixation duration. Results demonstrated that there was no difference amongst experts, and that trainees’ mean fixation duration was significantly shorter than experts and physicists’ fixation duration was significantly longer than that of the experts. Second, we evaluated spatial gaze deployment of the three viewer groups and quantified the difference between groups. Results showed that trainees and physicists deviated from where expert radiologists looked in images, and trainees performed better than physicists in terms of focusing on regions of interest. Finally, we investigated the saccadic behaviour of viewers and illustrated the differences between viewer groups in terms of saccade amplitudes and orientations.
•Gaze patterns can be used to differentiate radiologists from trainees or physicists•Physicists have higher dwell time than experts, trainees have lower dwell time•Trainees focus more on region of interests than physicists•Reader groups exhibit distinctive saccade amplitudes and orientations.
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