MuTILs: explainable, multiresolution computational scoring of Tumor-Infiltrating Lymphocytes in breast carcinomas using clinical guidelines

Tumor-Infiltrating Lymphocytes (TILs) have strong prognostic and predictive value in breast cancer, but their visual assessment is subjective. We present MuTILs, a convolutional neural network architecture specifically optimized for the assessment of TILs in whole-slide image scans in accordance with clinical scoring recommendations. MuTILs is a concept bottleneck model, designed to be explainable and to encourage sensible predictions at multiple resolutions. Our computational scores match visual scores and have independent prognostic value in invasive breast cancers from the TCGA dataset.

“Sometimes You Get Good Ones, and Sometimes You Get Not-so-Good Ones”: Vendors’ and Consumers’ Strategies to Identify and Mitigate Food Safety Risks in Urban Nigeria

This paper uses detailed data from in-depth interviews with consumers (n = 47) and vendors (n = 37) in three traditional markets in Birnin Kebbi, Nigeria. We used observations from those markets to examine how consumers and vendors identify and avoid or manage food safety risks and whom they hold responsible and trust when it comes to ensuring food safety. At the level of the vendor, consumers mentioned seeking “clean” or “neat” vendors or stalls. Cleanliness was primarily related to the appearance of the vendor, stall, and surroundings; reliance on trusted, known vendors was also noted. Food products themselves were largely evaluated based on visual cues: insects, holes, and colors—with some reliance on smell, also. Similarly, vendors assessed safety of food from suppliers based on a visual assessment or reliance on trusted relationships. On the second research question, both consumers and vendors largely placed responsibility for ensuring food safety on government; when asked specifically, consumers also named specific steps that vendors could take to ensure food safety. Consumers and vendors also generally felt that they could limit many food safety risks through identifying the “good” products in the market or from suppliers. The paper discusses the implications of these results for behavior change interventions.

Optimization of Spatial Resolution and Image Reconstruction Parameters for the Small-Animal MetisTM PET/CT System

The aim of this study was to investigate the optimization of spatial resolution and image reconstruction parameters related to image quality in an iterative reconstruction algorithm for the small-animal MetisTM PET/CT system. We used a homemade Derenzo phantom to evaluate the image quality by visual assessment, signal-to-noise ratio, contrast, coefficient of variation, and contrast-to-noise ratio of the 0.8 mm hot rods of 8 slices in the centre of the phantom PET images. A healthy mouse study was performed to analyze the influence of optimal reconstruction parameters and Gaussian post-filter FWHM. In the phantom study, the best image quality was obtained by placing the phantom at one end, keeping the central axis parallel to X-axis of the system, selecting iterations between 30 and 40, with a reconstruction voxel of 0.314 mm and a Gaussian post-filter FWHM of 1.57 mm. The optimization of spatial resolution can reach 0.6-mm. In the animal study, it was suitable to choose a voxel size of 0.472-mm, iterations between 30 and 40, and 2.36-mm Gaussian post-filter FWHM. Our results indicate that optimal imaging conditions and reconstruction parameters are necessary to obtain high-resolution images and quantitative accuracy, especially for the high-precision identification of tiny lesions.

The effect of Q.Clear reconstruction on quantification and spatial resolution of 18F-FDG PET in simultaneous PET/MR

Background Q.Clear is a block sequential regularized expectation maximization penalized-likelihood reconstruction algorithm for Positron Emission Tomography (PET). It has shown high potential in improving image reconstruction quality and quantification accuracy in PET/CT system. However, the evaluation of Q.Clear in PET/MR system, especially for clinical applications, is still rare. This study aimed to evaluate the impact of Q.Clear on the 18F-fluorodeoxyglucose (FDG) PET/MR system and to determine the optimal penalization factor β for clinical use. Methods A PET National Electrical Manufacturers Association/ International Electrotechnical Commission (NEMA/IEC) phantom was scanned on GE SIGNA PET/MR, based on NEMA NU 2-2012 standard. Metrics including contrast recovery (CR), background variability (BV), signal-to-noise ratio (SNR) and spatial resolution were evaluated for phantom data. For clinical data, lesion SNR, signal to background ratio (SBR), noise level and visual scores were evaluated. PET images reconstructed from OSEM + TOF and Q.Clear were visually compared and statistically analyzed, where OSEM + TOF adopted point spread function as default procedure, and Q.Clear used different β values of 100, 200, 300, 400, 500, 800, 1100 and 1400. Results For phantom data, as β value increased, CR and BV of all sizes of spheres decreased in general; images reconstructed from Q.Clear reached the peak SNR with β value of 400 and generally had better resolution than those from OSEM + TOF. For clinical data, compared with OSEM + TOF, Q.Clear with β value of 400 achieved 138% increment in median SNR (from 58.8 to 166.0), 59% increment in median SBR (from 4.2 to 6.8) and 38% decrement in median noise level (from 0.14 to 0.09). Based on visual assessment from two physicians, Q.Clear with β values ranging from 200 to 400 consistently achieved higher scores than OSEM + TOF, where β value of 400 was considered optimal. Conclusions The present study indicated that, on 18F-FDG PET/MR, Q.Clear reconstruction improved the image quality compared to OSEM + TOF. β value of 400 was optimal for Q.Clear reconstruction.

Falciform fat:femur length ratio provides a novel method for objective postmortem estimation of total body fat in overweight and obese cats

Determination of the nutritional condition, including estimation of amounts of total body fat (tBF), at routine postmortem examination of cats is typically based on subjective visual assessment. Subjective assessment may result in uncertainties regarding degree of overweight, and objective methods that provide a numerical value reflecting the tBF could be valuable to accurately judge excess body fat. We investigated if the falciform fat pad weight (FFPW) was correlated to tBF and could be used to detect overweight and obesity in cats. The FFPW and the femur length (FL) were recorded at postmortem examination in 54 cats and the FFPW:FL ratio (FFR) calculated. Each cat was additionally assigned to a fat category (FC) according to subjective assessment. Computed tomography was used to determine tBF as the body fat percentage (%BF), the body fat volume (BFV), and BFV normalized to animal size (nBFV) in 39 cats. There was strong correlation between the FFPW and the BFV ( r = 0.888) and between the FFR and the nBFV ( r = 0.897). The correlation between the nBFV and %BF was very strong ( r = 0.974). Using a lower FFR cutoff value of 3.5 for obesity and 1.6 for overweight, there was a discrepancy in FC between using the FFR and subjective assessment in 6 of 54 cats (11%). We conclude that the FFPW increases proportionally with tBF and that the FFR provides a method for objective tBF estimation. We suggest introducing the FFR to feline postmortem examination protocols as an objective estimate of tBF.

Localizing Epileptic Foci Before Surgery in Patients With MRI-Negative Refractory Epilepsy Using Statistical Parameter Mapping and Three-Dimensional Stereotactic Surface Projection Based on 18F-FDG PET

Patients with refractory epilepsy are not only free of seizures after resecting epileptic foci, but also experience significantly improved quality of life. Fluorine-18-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) is a promising avenue for detecting epileptic foci in patients with magnetic resonance imaging (MRI)-negative refractory epilepsy. However, the detection of epileptic foci by visual assessment based on 18F-FDG PET is often complicated by a variety of factors in clinical practice. Easy imaging methods based on 18F-FDG PET images, such as statistical parameter mapping (SPM) and three-dimensional stereotactic surface projection (3D-SSP), can objectively detect epileptic foci. In this study, the regions of surgical resection of patients with over 1 year follow-up and no seizures were defined as standard epileptic foci. We retrospectively analyzed the sensitivity of visual assessment, SPM and 3D-SSP based on 18F-FDG PET to detect epileptic foci in MRI-negative refractory epilepsy patients and obtained the sensitivities of visual assessment, SPM and 3D-SSP are 57, 70 and 60% respectively. Visual assessment combined with SPM or 3D-SSP can improve the sensitivity of detecting epileptic foci. The sensitivity was highest when the three methods were combined, but decreased consistency, in localizing epileptic foci. We conclude that SPM and 3D-SSP can be used as objective methods to detect epileptic foci before surgery in patients with MRI-negative refractory epilepsy. Visual assessment is the preferred method for PET image analysis in MRI-negative refractory epilepsy. When the visual assessment is inconsistent with the patient’s electroclinical information, SPM or 3D-SSP was further selected to assess the epileptic foci. If the combination of the two methods still fails to accurately locate the epileptic foci, comprehensive evaluation can be performed by combining the three methods.

Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma

Background: Ki-67 is a widely used proliferation marker reflecting prognosis in various tumors. However, visual assessment and scoring of Ki-67 suffers from marked inter-observer and intra-observer variability. We aimed to assess the concordance of manual counting and automated image-analytic scoring methods for Ki-67 in synovial sarcoma. Patients and Methods: Tissue microarrays from 34 patients with synovial sarcoma were immunostained for Ki-67 and scored both visually and with 3DHistech QuantCenter. Results: The automated assessment of Ki-67 expression was in good agreement with the visually counted Ki-67 (rPearson=0.96, p<0.001). In a Cox regression model automated [hazard ratio (HR)=1.047, p=0.024], but not visual (HR=1.063, p=0.053) assessment method associated high Ki-67 scores with worse overall survival. Conclusion: The automated Ki-67 assessment method appears to be comparable to the visual method in synovial sarcoma and had a significant association to overall survival.

Investigating the Possibility of Determining the Sequence Intersecting Lines between LaserJet Printing and Handwriting in Document Examination using Color Measurement Technique

In Questioned Documents Examination, the sequence of crossing lines in the intersection of handwriting and printed area can be important clues for detecting tampered documents. Recognition of such documents is a arduous task and requires people with experience and expertise. In the present work, we investigated the possibility of determining the sequence of intersecting lines between LaserJet printing and handwriting for a series of simulated laboratory specimens in the document examination using color measurement technique. The spectral reflectance curves and color coordinates of some points on and out of the cross lines were compared. Four different commercial ballpoint pens and a black toner LaserJet were used to prepare the specimens. The color change of the intersecting lines was subjectively considered through the captured images and a visual assessment process. It was also objectively determined by determining the color difference values from the colorimetric data in CIELAB and CIELCH color spaces in the visible range. The color change evaluation showed that the order in which printing or handwriting is applied alters colorimetric results. Moreover, the investigations showed small color difference values of less than 2 units between a point of printed area individually, and intersection could be applied as a tolerance limit for pass/fail judgments.