Impact of Stain Normalization on Pathologist Assessment of Prostate Cancer: A Comparative Study.

In clinical routine, the quality of whole-slide images plays a key role in the pathologist's diagnosis, and suboptimal staining may be a limiting factor. The stain normalization process helps to solve this problem through the standardization of color appearance of a source image with respect to a target image with optimal chromatic features. The analysis is focused on the evaluation of the following parameters assessed by two experts on original and normalized slides: (i) perceived color quality, (ii) diagnosis for the patient, (iii) diagnostic confidence and (iv) time required for diagnosis. Results show a statistically significant increase in color quality in the normalized images for both experts (p < 0.0001). Regarding prostate cancer assessment, the average times for diagnosis are significantly lower for normalized images than original ones (first expert: 69.9 s vs. 77.9 s with p < 0.0001; second expert: 37.4 s vs. 52.7 s with p < 0.0001), and at the same time, a statistically significant increase in diagnostic confidence is proven. The improvement of poor-quality images and greater clarity of diagnostically important details in normalized slides demonstrate the potential of stain normalization in the routine practice of prostate cancer assessment.

Beyond alpha-band: The neural correlate of creative thinking.

The compound nature of creativity entails the interplay of multiple cognitive processes, making it difficult to attribute creativity to a single neural signature. Divergent thinking paradigms, widely adopted to investigate creative production, have highlighted the key role of specific mental operations subserving creativity, such as inhibition of external stimuli, loose semantic associations, and mental imagery. Neurophysiological studies have typically shown a high alpha rhythm synchronization when individuals are engaged in creative ideation. Also, oculomotor activity and pupil diameter have been proposed as useful indicators of mental operations involved in such a thinking process. The goal of this study was to investigate whether beyond alpha-band activity other higher frequency bands, such as beta and gamma, may subserve divergent and convergent thinking and whether those could be associated with a different gaze bias and pupil response during ideas generation. Implementing a within-subjects design we collected behavioral measures, neural activity, gaze patterns, and pupil dilation while participants performed a revised version of the Alternative Uses Task, in which divergent thinking is contrasted to convergent thinking. As expected, participants took longer to generate creative ideas as compared to common ones. Interestingly, during divergent thinking participants displayed alpha synchronization along with beta and gamma desynchronization, more pronounced leftward gaze shift, and greater pupil dilation. During convergent thinking, an opposite pattern was observed: desynchronization in alpha and an increase in beta and gamma rhythm, along with a reduction of leftward gaze shift and greater pupil constriction. The present study uncovered specific neural dynamics and physiological patterns during idea generation, providing novel insight into the complex physiological signature of creative production.

Stain normalization in digital pathology: Clinical multi-center evaluation of image quality.

In digital pathology, the final appearance of digitized images is affected by several factors, resulting in stain color and intensity variation. Stain normalization is an innovative solution to overcome stain variability. However, the validation of color normalization tools has been assessed only from a quantitative perspective, through the computation of similarity metrics between the original and normalized images. To the best of our knowledge, no works investigate the impact of normalization on the pathologist's evaluation. The objective of this paper is to propose a multi-tissue (i.e., breast, colon, liver, lung, and prostate) and multi-center qualitative analysis of a stain normalization tool with the involvement of pathologists with different years of experience. Two qualitative studies were carried out for this purpose: (i) a first study focused on the analysis of the perceived image quality and absence of significant image artifacts after the normalization process; (ii) a second study focused on the clinical score of the normalized image with respect to the original one. The results of the first study prove the high quality of the normalized image with a low impact artifact generation, while the second study demonstrates the superiority of the normalized image with respect to the original one in clinical practice. The normalization process can help both to reduce variability due to tissue staining procedures and facilitate the pathologist in the histological examination. The experimental results obtained in this work are encouraging and can justify the use of a stain normalization tool in clinical routine.

Stain Color Adaptive Normalization (SCAN) algorithm: Separation and standardization of histological stains in digital pathology.

BACKGROUND AND OBJECTIVE: The diagnosis of histopathological images is based on the visual analysis of tissue slices under a light microscope. However, the histological tissue appearance may assume different color intensities depending on the staining process, operator ability and scanner specifications. This stain variability affects the diagnosis of the pathologist and decreases the accuracy of computer-aided diagnosis systems. In this context, the stain normalization process has proved to be a powerful tool to cope with this issue, allowing to standardize the stain color appearance of a source image respect to a reference image. METHODS: In this paper, novel fully automated stain separation and normalization approaches for hematoxylin and eosin stained histological slides are presented. The proposed algorithm, named SCAN (Stain Color Adaptive Normalization), is based on segmentation and clustering strategies for cellular structures detection. The SCAN algorithm is able to improve the contrast between histological tissue and background and preserve local structures without changing the color of the lumen and the background. RESULTS: Both stain separation and normalization techniques were qualitatively and quantitively validated on a multi-tissue and multiscale dataset, with highly satisfactory results, outperforming the state-of-the-art approaches. SCAN was also tested on whole-slide images with high performances and low computational times. CONCLUSIONS: The potential contribution of the proposed standardization approach is twofold: the improvement of visual diagnosis in digital histopathology and the development of powerful pre-processing strategies to automated classification techniques for cancer detection.

Automatic Optic Nerve Measurement: A New Tool to Standardize Optic Nerve Assessment in Ultrasound B-Mode Images.

Transorbital sonography provides reliable information about the estimation of intra-cranial pressure by measuring the optic nerve sheath diameter (ONSD), whereas the optic nerve (ON) diameter (OND) may reveal ON atrophy in patients with multiple sclerosis. Here, an AUTomatic Optic Nerve MeAsurement (AUTONoMA) system for OND and ONSD assessment in ultrasound B-mode images based on deformable models is presented. The automated measurements were compared with manual ones obtained by two operators, with no significant differences. AUTONoMA correctly segmented the ON and its sheath in 71 out of 75 images. The mean error compared with the expert operator was 0.06 ± 0.52 mm and 0.06 ± 0.35 mm for the ONSD and OND, respectively. The agreement between operators and AUTONoMA was good and a positive correlation was found between the readers and the algorithm with errors comparable with the inter-operator variability. The AUTONoMA system may allow for standardization of OND and ONSD measurements, reducing manual evaluation variability.

Cascaded LSTM recurrent neural network for automated sleep stage classification using single-channel EEG signals.

Automated evaluation of a subject's neurocognitive performance (NCP) is a relevant topic in neurological and clinical studies. NCP represents the mental/cognitive human capacity in performing a specific task. It is difficult to develop the study protocols as the subject's NCP changes in a known predictable way. Sleep is time-varying NCP and can be used to develop novel NCP techniques. Accurate analysis and interpretation of human sleep electroencephalographic (EEG) signals is needed for proper NCP assessment. In addition, sleep deprivation may cause prominent cognitive risks in performing many common activities such as driving or controlling a generic device; therefore, sleep scoring is a crucial part of the process. In the sleep cycle, the first stage of non-rapid eye movement (NREM) sleep or stage N1 is the transition between wakefulness and drowsiness and becomes relevant for the study of NCP. In this study, a novel cascaded recurrent neural network (RNN) architecture based on long short-term memory (LSTM) blocks, is proposed for the automated scoring of sleep stages using EEG signals derived from a single-channel. Fifty-five time and frequency-domain features were extracted from the EEG signals and fed to feature reduction algorithms to select the most relevant ones. The selected features constituted as the inputs to the LSTM networks. The cascaded architecture is composed of two LSTM RNNs: the first network performed 4-class classification (i.e. the five sleep stages with the merging of stages N1 and REM into a single stage) with a classification rate of 90.8%, and the second one obtained a recognition performance of 83.6% for 2-class classification (i.e. N1 vs REM). The overall percentage of correct classification for five sleep stages is found to be 86.7%. The objective of this work is to improve classification performance in sleep stage N1, as a first step of NCP assessment, and at the same time obtain satisfactory classification results in the other sleep stages.

Automatic Extraction of Dermatological Parameters from Nevi Using an Inexpensive Smartphone Microscope: A Proof of Concept.

The evolution of smartphone technology has made their use more common in dermatological applications. Here we studied the feasibility of using an inexpensive smartphone microscope for the extraction of dermatological parameters and compared the results obtained with a portable dermoscope, commonly used in clinical practice. Forty-two skin lesions were imaged with both devices and visually analyzed by an expert dermatologist. The presence of a reticular pattern was observed in 22 dermoscopic images, but only in 10 smartphone images. The proposed paradigm segments the image and extracts texture features which are used to train and validate a neural network to classify the presence of a reticular pattern. Using 5-fold cross-validation, an accuracy of 100% and 95% was obtained with the dermoscopic and smartphone images, respectively. This approach can be useful for general practitioners and as a triage tool for skin lesion analysis.

Non-invasive analysis of actinic keratosis using a cold stimulation and near-infrared spectroscopy.

Non-melanoma skin cancers are the most common tumor in the Caucasian population, and include actinic keratosis (AK), which is considered an early form of in-situ squamous cell carcinoma (SCC). Currently the only way to monitor lesion progression (i.e., from AK to invasive SCC) is through an invasive bioptic procedure. Near-infrared spectroscopy (NIRS) is a non-invasive technique that studies haemoglobin (oxygenated haemoglobin, O2Hb, and deoxygenated haemoglobin, HHb) relative concentration variations. The objective of this study is to evaluate if AKs present a different vascular response when compared to healthy skin using time and frequency parameters extracted from the NIRS signals. The NIRS signals were acquired on the AKs and a healthy skin area of patients (n=53), with the same acquisition protocol: baseline signals (1.5 min), application of ice pack near lesion (1.5 min), removal of ice pack and acquisition of vascular recovery (1.5 min). We calculated 18 features to evaluate if the vascular response was different in the two cases (i.e., healthy skin and AK lesions). By applying the multivariate analysis of variance (MANOVA), a statistically significant difference is found in the O2Hb and HHb after the stimulus application. This shows how the NIRS technique can give important vascular information that could help the diagnosis of a lesion and the evaluation of its progression. Overall, the obtained results encourage us to look further into the study of the skin lesions and their progression with NIRS signals.

Multimodal T2w and DWI Prostate Gland Automated Registration.

Multiparametric magnetic resonance imaging (mpMRI) is emerging as a promising tool in the clinical pathway of prostate cancer (PCa). The registration between a structural and a functional imaging modality, such as T2-weighted (T2w) and diffusion-weighted imaging (DWI) is fundamental in the development of a mpMRI-based computer aided diagnosis (CAD) system for PCa. Here, we propose an automated method to register the prostate gland in T2w and DWI image sequences by a landmark-based affine registration and a non-parametric diffeomorphic registration. An expert operator manually segmented the prostate gland in both modalities on a dataset of 20 patients. Target registration error and Jaccard index, which measures the overlap between masks, were evaluated pre- and post- registration resulting in an improvement of 44% and 21%, respectively. In the future, the proposed method could be useful in the framework of a CAD system for PCa detection and characterization in mpMRI.