White adipose tissue distribution and amount are associated with increased white matter connectivity.

Obesity represents a significant public health concern and is linked to various comorbidities and cognitive impairments. Previous research indicates that elevated body mass index (BMI) is associated with structural changes in white matter (WM). However, a deeper characterization of body composition is required, especially considering the links between abdominal obesity and metabolic dysfunction. This study aims to enhance our understanding of the relationship between obesity and WM connectivity by directly assessing the amount and distribution of fat tissue. Whole-body magnetic resonance imaging (MRI) was employed to evaluate total adipose tissue (TAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), while MR liver spectroscopy measured liver fat content in 63 normal-weight, overweight, and obese males. WM connectivity was quantified using microstructure-informed tractography. Connectome-based predictive modeling was used to predict body composition metrics based on WM connectomes. Our analysis revealed a positive dependency between BMI, TAT, SAT, and WM connectivity in brain regions involved in reward processing and appetite regulation, such as the insula, nucleus accumbens, and orbitofrontal cortex. Increased connectivity was also observed in cognitive control and inhibition networks, including the middle frontal gyrus and anterior cingulate cortex. No significant associations were found between WM connectivity and VAT or liver fat. Our findings suggest that altered neural communication between these brain regions may affect cognitive processes, emotional regulation, and reward perception in individuals with obesity, potentially contributing to weight gain. While our study did not identify a link between WM connectivity and VAT or liver fat, further investigation of the role of various fat depots and metabolic factors in brain networks is required to advance obesity prevention and treatment approaches.

Accuracy and Reliability of Pelvimetry Measures Obtained by Manual or Automatic Labeling of Three-Dimensional Pelvic Models.

(1) Background: The morphology of the pelvic cavity is important for decision-making in obstetrics. This study aimed to estimate the accuracy and reliability of pelvimetry measures obtained when radiologists manually label anatomical landmarks on three-dimensional (3D) pelvic models. A second objective was to design an automatic labeling method. (2) Methods: Three operators segmented 10 computed tomography scans each. Three radiologists then labeled 12 anatomical landmarks on the pelvic models, which allowed for the calculation of 15 pelvimetry measures. Additionally, an automatic labeling method was developed based on a reference pelvic model, including reference anatomical landmarks, matching the individual pelvic models. (3) Results: Heterogeneity among landmarks in radiologists' labeling accuracy was observed, with some landmarks being rarely mislabeled by more than 4 mm and others being frequently mislabeled by 10 mm or more. The propagation to the pelvimetry measures was limited; only one out of the 15 measures reported a median error above 5 mm or 5°, and all measures showed moderate to excellent inter-radiologist reliability. The automatic method outperformed manual labeling. (4) Conclusions: This study confirmed the suitability of pelvimetry measures based on manual labeling of 3D pelvic models. Automatic labeling offers promising perspectives to decrease the demand on radiologists, standardize the labeling, and describe the pelvic cavity in more detail.

Distill-SODA: Distilling Self-Supervised Vision Transformer for Source-Free Open-Set Domain Adaptation in Computational Pathology.

Developing computational pathology models is essential for reducing manual tissue typing from whole slide images, transferring knowledge from the source domain to an unlabeled, shifted target domain, and identifying unseen categories. We propose a practical setting by addressing the above-mentioned challenges in one fell swoop, i.e., source-free open-set domain adaptation. Our methodology focuses on adapting a pre-trained source model to an unlabeled target dataset and encompasses both closed-set and open-set classes. Beyond addressing the semantic shift of unknown classes, our framework also deals with a covariate shift, which manifests as variations in color appearance between source and target tissue samples. Our method hinges on distilling knowledge from a self-supervised vision transformer (ViT), drawing guidance from either robustly pre-trained transformer models or histopathology datasets, including those from the target domain. In pursuit of this, we introduce a novel style-based adversarial data augmentation, serving as hard positives for self-training a ViT, resulting in highly contextualized embeddings. Following this, we cluster semantically akin target images, with the source model offering weak pseudo-labels, albeit with uncertain confidence. To enhance this process, we present the closed-set affinity score (CSAS), aiming to correct the confidence levels of these pseudo-labels and to calculate weighted class prototypes within the contextualized embedding space. Our approach establishes itself as state-of-the-art across three public histopathological datasets for colorectal cancer assessment. Notably, our self-training method seamlessly integrates with open-set detection methods, resulting in enhanced performance in both closed-set and open-set recognition tasks.

The influence of cardiac arrhythmias on the detection of heartbeats in the photoplethysmogram: benchmarking open-source algorithms.

Objective.Cardiac arrhythmias are a leading cause of mortality worldwide. Wearable devices based on photoplethysmography give the opportunity to screen large populations, hence allowing for an earlier detection of pathological rhythms that might reduce the risks of complications and medical costs. While most of beat detection algorithms have been evaluated on normal sinus rhythm or atrial fibrillation recordings, the performance of these algorithms in patients with other cardiac arrhythmias, such as ventricular tachycardia or bigeminy, remain unknown to date.Approach. ThePPG-beatsopen-source framework, developed by Charlton and colleagues, evaluates the performance of the beat detectors namedQPPG,MSPTDandABDamong others. We applied thePPG-beatsframework on two newly acquired datasets, one containing seven different types of cardiac arrhythmia in hospital settings, and another dataset including two cardiac arrhythmias in ambulatory settings.Main Results. In a clinical setting, theQPPGbeat detector performed best on atrial fibrillation (with a medianF1score of 94.4%), atrial flutter (95.2%), atrial tachycardia (87.0%), sinus rhythm (97.7%), ventricular tachycardia (83.9%) and was ranked 2nd for bigeminy (75.7%) behindABDdetector (76.1%). In an ambulatory setting, theMSPTDbeat detector performed best on normal sinus rhythm (94.6%), and theQPPGdetector on atrial fibrillation (91.6%) and bigeminy (80.0%).Significance. Overall, the PPG beat detectorsQPPG,MSPTDandABDconsistently achieved higher performances than other detectors. However, the detection of beats from wrist-PPG signals is compromised in presence of bigeminy or ventricular tachycardia.

Pore size estimation in axon-mimicking microfibers with diffusion-relaxation MRI.

PURPOSE: This study aims to evaluate two distinct approaches for fiber radius estimation using diffusion-relaxation MRI data acquired in biomimetic microfiber phantoms that mimic hollow axons. The methods considered are the spherical mean power-law approach and a T2-based pore size estimation technique. THEORY AND METHODS: A general diffusion-relaxation theoretical model for the spherical mean signal from water molecules within a distribution of cylinders with varying radii was introduced, encompassing the evaluated models as particular cases. Additionally, a new numerical approach was presented for estimating effective radii (i.e., MRI-visible mean radii) from the ground truth radii distributions, not reliant on previous theoretical approximations and adaptable to various acquisition sequences. The ground truth radii were obtained from scanning electron microscope images. RESULTS: Both methods show a linear relationship between effective radii estimated from MRI data and ground-truth radii distributions, although some discrepancies were observed. The spherical mean power-law method overestimated fiber radii. Conversely, the T2-based method exhibited higher sensitivity to smaller fiber radii, but faced limitations in accurately estimating the radius in one particular phantom, possibly because of material-specific relaxation changes. CONCLUSION: The study demonstrates the feasibility of both techniques to predict pore sizes of hollow microfibers. The T2-based technique, unlike the spherical mean power-law method, does not demand ultra-high diffusion gradients, but requires calibration with known radius distributions. This research contributes to the ongoing development and evaluation of neuroimaging techniques for fiber radius estimation, highlights the advantages and limitations of both methods, and provides datasets for reproducible research.

Windowed Radon Transform and Tensor Rank-1 Decomposition for Adaptive Beamforming in Ultrafast Ultrasound.

Ultrafast ultrasound has recently emerged as an alternative to traditional focused ultrasound. By virtue of the low number of insonifications it requires, ultrafast ultrasound enables the imaging of the human body at potentially very high frame rates. However, unaccounted for speed-of-sound variations in the insonified medium often result in phase aberrations in the reconstructed images. The diagnosis capability of ultrafast ultrasound is thus ultimately impeded. Therefore, there is a strong need for adaptive beamforming methods that are resilient to speed-of-sound aberrations. Several of such techniques have been proposed recently but they often lack parallelizability or the ability to directly correct both transmit and receive phase aberrations. In this article, we introduce an adaptive beamforming method designed to address these shortcomings. To do so, we compute the windowed Radon transform of several complex radio-frequency images reconstructed using delay-and-sum. Then, we apply to the obtained local sinograms weighted tensor rank-1 decompositions and their results are eventually used to reconstruct a corrected image. We demonstrate using simulated and in-vitro data that our method is able to successfully recover aberration-free images and that it outperforms both coherent compounding and the recently introduced SVD beamformer. Finally, we validate the proposed beamforming technique on in-vivo data, resulting in a significant improvement of image quality compared to the two reference methods.

Tract-wise microstructural analysis informs on current and future disability in early multiple sclerosis.

OBJECTIVES: Microstructural characterization of patients with multiple sclerosis (MS) has been shown to correlate better with disability compared to conventional radiological biomarkers. Quantitative MRI provides effective means to characterize microstructural brain tissue changes both in lesions and normal-appearing brain tissue. However, the impact of the location of microstructural alterations in terms of neuronal pathways has not been thoroughly explored so far. Here, we study the extent and the location of tissue changes probed using quantitative MRI along white matter (WM) tracts extracted from a connectivity atlas. METHODS: We quantified voxel-wise T1 tissue alterations compared to normative values in a cohort of 99 MS patients. For each WM tract, we extracted metrics reflecting tissue alterations both in lesions and normal-appearing WM and correlated these with cross-sectional disability and disability evolution after 2 years. RESULTS: In early MS patients, T1 alterations in normal-appearing WM correlated better with disability evolution compared to cross-sectional disability. Further, the presence of lesions in supratentorial tracts was more strongly associated with cross-sectional disability, while microstructural alterations in infratentorial pathways yielded higher correlations with disability evolution. In progressive patients, all major WM pathways contributed similarly to explaining disability, and correlations with disability evolution were generally poor. CONCLUSIONS: We showed that microstructural changes evaluated in specific WM pathways contribute to explaining future disability in early MS, hence highlighting the potential of tract-wise analyses in monitoring disease progression. Further, the proposed technique allows to estimate WM tract-specific microstructural characteristics in clinically compatible acquisition times, without the need for advanced diffusion imaging.

Windowed Radon Transform for Robust Speed-of-Sound Imaging With Pulse-Echo Ultrasound.

In recent years, methods estimating the spatial distribution of tissue speed of sound with pulse-echo ultrasound are gaining considerable traction. They can address limitations of B-mode imaging, for instance in diagnosing fatty liver diseases. Current state-of-the-art methods relate the tissue speed of sound to local echo shifts computed between images that are beamformed using restricted transmit and receive apertures. However, the aperture limitation affects the robustness of phase-shift estimations and, consequently, the accuracy of reconstructed speed-of-sound maps. Here, we propose a method based on the Radon transform of image patches able to estimate local phase shifts from full-aperture images. We validate our technique on simulated, phantom and in-vivo data acquired on a liver and compare it with a state-of-the-art method. We show that the proposed method enhances the stability to changes of beamforming speed of sound and to a reduction of the number of insonifications. In particular, the deployment of pulse-echo speed-of-sound estimation methods onto portable ultrasound devices can be eased by the reduction of the number of insonifications allowed by the proposed method.

Self-supervised learning-based cervical cytology for the triage of HPV-positive women in resource-limited settings and low-data regime.

Screening Papanicolaou test samples has proven to be highly effective in reducing cervical cancer-related mortality. However, the lack of trained cytopathologists hinders its widespread implementation in low-resource settings. Deep learning-assisted telecytology diagnosis emerges as an appealing alternative, but it requires the collection of large annotated training datasets, which is costly and time-consuming. In this paper, we demonstrate that the abundance of unlabeled images that can be extracted from Pap smear test whole slide images presents a fertile ground for self-supervised learning methods, yielding performance improvements compared to off-the-shelf pre-trained models for various downstream tasks. In particular, we propose Cervical Cell Copy-Pasting (C3P) as an effective augmentation method, which enables knowledge transfer from public and labeled single-cell datasets to unlabeled tiles. Not only does C3P outperforms naive transfer from single-cell images, but we also demonstrate its advantageous integration into multiple instance learning methods. Importantly, all our experiments are conducted on our introduced in-house dataset comprising liquid-based cytology Pap smear images obtained using low-cost technologies. This aligns with our long-term objective of deep learning-assisted telecytology for diagnosis in low-resource settings.

A KL Divergence-Based Loss for In Vivo Ultrafast Ultrasound Image Enhancement with Deep Learning.

Ultrafast ultrasound imaging, characterized by high frame rates, generates low-quality images. Convolutional neural networks (CNNs) have demonstrated great potential to enhance image quality without compromising the frame rate. However, CNNs have been mostly trained on simulated or phantom images, leading to suboptimal performance on in vivo images. In this study, we present a method to enhance the quality of single plane wave (PW) acquisitions using a CNN trained on in vivo images. Our contribution is twofold. Firstly, we introduce a training loss function that accounts for the high dynamic range of the radio frequency data and uses the Kullback-Leibler divergence to preserve the probability distributions of the echogenicity values. Secondly, we conduct an extensive performance analysis on a large new in vivo dataset of 20,000 images, comparing the predicted images to the target images resulting from the coherent compounding of 87 PWs. Applying a volunteer-based dataset split, the peak signal-to-noise ratio and structural similarity index measure increase, respectively, from 16.466 ± 0.801 dB and 0.105 ± 0.060, calculated between the single PW and target images, to 20.292 ± 0.307 dB and 0.272 ± 0.040, between predicted and target images. Our results demonstrate significant improvements in image quality, effectively reducing artifacts.

Molecular Imaging with Aquaporin-Based Reporter Genes: Quantitative Considerations from Monte Carlo Diffusion Simulations.

Aquaporins provide a unique approach for imaging genetic activity in deep tissues by increasing the rate of cellular water diffusion, which generates a magnetic resonance contrast. However, distinguishing aquaporin signals from the tissue background is challenging because water diffusion is influenced by structural factors, such as cell size and packing density. Here, we developed a Monte Carlo model to analyze how cell radius and intracellular volume fraction quantitatively affect aquaporin signals. We demonstrated that a differential imaging approach based on subtracting signals at two diffusion times can improve specificity by unambiguously isolating aquaporin signals from the tissue background. We further used Monte Carlo simulations to analyze the connection between diffusivity and the percentage of cells engineered to express aquaporin and established a mapping that accurately determined the volume fraction of aquaporin-expressing cells in mixed populations. The quantitative framework developed in this study will enable a broad range of applications in biomedical synthetic biology, requiring the use of aquaporins to noninvasively monitor the location and function of genetically engineered devices in live animals.

CACTUS: a computational framework for generating realistic white matter microstructure substrates.

Monte-Carlo diffusion simulations are a powerful tool for validating tissue microstructure models by generating synthetic diffusion-weighted magnetic resonance images (DW-MRI) in controlled environments. This is fundamental for understanding the link between micrometre-scale tissue properties and DW-MRI signals measured at the millimetre-scale, optimizing acquisition protocols to target microstructure properties of interest, and exploring the robustness and accuracy of estimation methods. However, accurate simulations require substrates that reflect the main microstructural features of the studied tissue. To address this challenge, we introduce a novel computational workflow, CACTUS (Computational Axonal Configurator for Tailored and Ultradense Substrates), for generating synthetic white matter substrates. Our approach allows constructing substrates with higher packing density than existing methods, up to 95% intra-axonal volume fraction, and larger voxel sizes of up to 500µm3 with rich fibre complexity. CACTUS generates bundles with angular dispersion, bundle crossings, and variations along the fibres of their inner and outer radii and g-ratio. We achieve this by introducing a novel global cost function and a fibre radial growth approach that allows substrates to match predefined targeted characteristics and mirror those reported in histological studies. CACTUS improves the development of complex synthetic substrates, paving the way for future applications in microstructure imaging.

Estimating axon radius using diffusion-relaxation MRI: calibrating a surface-based relaxation model with histology.

Axon radius is a potential biomarker for brain diseases and a crucial tissue microstructure parameter that determines the speed of action potentials. Diffusion MRI (dMRI) allows non-invasive estimation of axon radius, but accurately estimating the radius of axons in the human brain is challenging. Most axons in the brain have a radius below one micrometer, which falls below the sensitivity limit of dMRI signals even when using the most advanced human MRI scanners. Therefore, new MRI methods that are sensitive to small axon radii are needed. In this proof-of-concept investigation, we examine whether a surface-based axonal relaxation process could mediate a relationship between intra-axonal T2 and T1 times and inner axon radius, as measured using postmortem histology. A unique in vivo human diffusion-T1-T2 relaxation dataset was acquired on a 3T MRI scanner with ultra-strong diffusion gradients, using a strong diffusion-weighting (i.e., b = 6,000 s/mm2) and multiple inversion and echo times. A second reduced diffusion-T2 dataset was collected at various echo times to evaluate the model further. The intra-axonal relaxation times were estimated by fitting a diffusion-relaxation model to the orientation-averaged spherical mean signals. Our analysis revealed that the proposed surface-based relaxation model effectively explains the relationship between the estimated relaxation times and the histological axon radius measured in various corpus callosum regions. Using these histological values, we developed a novel calibration approach to predict axon radius in other areas of the corpus callosum. Notably, the predicted radii and those determined from histological measurements were in close agreement.

Computer vision-based algorithm to sUppoRt coRrect electrode placemeNT (CURRENT) for home-based electric non-invasive brain stimulation.

OBJECTIVE: Home-based non-invasive brain stimulation (NIBS) has been suggested as an adjunct treatment strategy for neuro-psychiatric disorders. There are currently no available solutions to direct and monitor correct placement of the stimulation electrodes. To address this issue, we propose an easy-to-use digital tool to support patients for self-application. METHODS: We recruited 36 healthy participants and compared their cap placement performance with the one of a NIBS-expert investigator. We tested participants' placement accuracy with instructions before (Pre) and after the investigator's placement (Post), as well as participants using the support tool (CURRENT). User experience (UX) and confidence were further evaluated. RESULTS: Permutation tests demonstrated a smaller deviation within the CURRENT compared with Pre cap placement (p = 0.02). Subjective evaluation of ease of use and usefulness of the tool were vastly positive (8.04 out of 10). CURRENT decreased the variability of performance, ensured placement within the suggested maximum of deviation (10 mm) and supported confidence of correct placement. CONCLUSIONS: This study supports the usability of this novel technology for correct electrode placement during self-application in home-based settings. SIGNIFICANCE: CURRENT provides an exciting opportunity to promote home-based, self-applied NIBS as a safe, high-frequency treatment strategy that can be well integrated in patients' daily lives.

Cellular Exchange Imaging (CEXI): Evaluation of a diffusion model including water exchange in cells using numerical phantoms of permeable spheres.

PURPOSE: Biophysical models of diffusion MRI have been developed to characterize microstructure in various tissues, but existing models are not suitable for tissue composed of permeable spherical cells. In this study we introduce Cellular Exchange Imaging (CEXI), a model tailored for permeable spherical cells, and compares its performance to a related Ball & Sphere (BS) model that neglects permeability. METHODS: We generated DW-MRI signals using Monte-Carlo simulations with a PGSE sequence in numerical substrates made of spherical cells and their extracellular space for a range of membrane permeability. From these signals, the properties of the substrates were inferred using both BS and CEXI models. RESULTS: CEXI outperformed the impermeable model by providing more stable estimates cell size and intracellular volume fraction that were diffusion time-independent. Notably, CEXI accurately estimated the exchange time for low to moderate permeability levels previously reported in other studies ( κ < 25 µ m / s $$ \kappa <25\kern0.3em \mu \mathrm{m}/\mathrm{s} $$ ). However, in highly permeable substrates ( κ = 50 µ m / s $$ \kappa =50\kern0.3em \mu \mathrm{m}/\mathrm{s} $$ ), the estimated parameters were less stable, particularly the diffusion coefficients. CONCLUSION: This study highlights the importance of modeling the exchange time to accurately quantify microstructure properties in permeable cellular substrates. Future studies should evaluate CEXI in clinical applications such as lymph nodes, investigate exchange time as a potential biomarker of tumor severity, and develop more appropriate tissue models that account for anisotropic diffusion and highly permeable membranes.

Cortical alterations after very preterm birth and the association with socio-emotional abilities from childhood to early adolescence.

Very preterm birth (VPT; <32 weeks' gestation) leads to a situation where crucial steps of brain development occur in an abnormal ex utero environment, translating to vulnerable cortical and subcortical development. Associated with this atypical brain development, children and adolescents born VPT are at a high risk of socio-emotional difficulties. In the current study, we unravel developmental changes in cortical gray matter (GM) concentration in VPT and term-born controls aged 6-14 years, together with their associations with socio-emotional abilities. T1-weighted images were used to estimate signal intensities of brain tissue types in a single voxel (GM, white matter, and cortico-spinal fluid) and extract GM concentration disentangled from the presence of partial volume effects (PVEs). General linear model analysis was used to compare groups. Socio-emotional abilities were assessed and associations with GM concentration were explored using univariate and multivariate analyses. The effects of prematurity were far-reaching, with intricated patterns of increases and decreases of GM concentration mainly in frontal, temporal, parietal, and cingular regions. Better socio-emotional abilities were associated with increased GM concentration in regions known to be involved in such process for both groups. Our findings suggest that the trajectory of brain development following VPT birth may be fundamentally distinctive and impact socio-emotional abilities.

Molecular imaging with aquaporin-based reporter genes: quantitative considerations from Monte Carlo diffusion simulations.

Aquaporins provide a new class of genetic tools for imaging molecular activity in deep tissues by increasing the rate of cellular water diffusion, which generates magnetic resonance contrast. However, distinguishing aquaporin contrast from the tissue background is challenging because water diffusion is also influenced by structural factors such as cell size and packing density. Here, we developed and experimentally validated a Monte Carlo model to analyze how cell radius and intracellular volume fraction quantitatively affect aquaporin signals. We demonstrated that a differential imaging approach based on time-dependent changes in diffusivity can improve specificity by unambiguously isolating aquaporin-driven contrast from the tissue background. Finally, we used Monte Carlo simulations to analyze the connection between diffusivity and the percentage of cells engineered to express aquaporin, and established a simple mapping that accurately determined the volume fraction of aquaporin-expressing cells in mixed populations. This study creates a framework for broad applications of aquaporins, particularly in biomedicine and in vivo synthetic biology, where quantitative methods to measure the location and performance of genetic devices in whole vertebrates are necessary.

Refraction-Based Speed of Sound Estimation in Layered Media: An Angular Approach.

Speed of sound estimation in ultrasound imaging is a growing modality with several clinical applications such as hepatic steatosis stages quantification. A key challenge for clinically relevant speed of sound estimation is to obtain repeatable values independent of superficial tissues and available in real-time. Recent works have demonstrated the feasibility to achieve quantitative estimations of the local speed of sound in layered media. However, such techniques require high computational power and exhibit instabilities. We present a novel speed of sound estimation technique based on an angular approach of ultrasound imaging in which plane waves are considered in transmit and receive. This change of paradigm allows us to rely on the refraction properties of plane waves to infer the local speed of sound values directly from the angular raw data. The proposed method robustly estimates the local speed of sound with only a few ultrasound emissions and with a low computational complexity which makes it compatible with real-time imaging. Simulations and in vitro experimental results show that the proposed method outperforms state-of-the-art approaches with biases and standard deviations lower than 10 m s-1, eight times fewer emissions, and 1000 times lower computational time. Further in vivo experiments validate its performance for liver imaging.

Artificial Intelligence-Based Cervical Cancer Screening on Images Taken during Visual Inspection with Acetic Acid: A Systematic Review.

Visual inspection with acetic acid (VIA) is one of the methods recommended by the World Health Organization for cervical cancer screening. VIA is simple and low-cost; it, however, presents high subjectivity. We conducted a systematic literature search in PubMed, Google Scholar and Scopus to identify automated algorithms for classifying images taken during VIA as negative (healthy/benign) or precancerous/cancerous. Of the 2608 studies identified, 11 met the inclusion criteria. The algorithm with the highest accuracy in each study was selected, and some of its key features were analyzed. Data analysis and comparison between the algorithms were conducted, in terms of sensitivity and specificity, ranging from 0.22 to 0.93 and 0.67 to 0.95, respectively. The quality and risk of each study were assessed following the QUADAS-2 guidelines. Artificial intelligence-based cervical cancer screening algorithms have the potential to become a key tool for supporting cervical cancer screening, especially in settings where there is a lack of healthcare infrastructure and trained personnel. The presented studies, however, assess their algorithms using small datasets of highly selected images, not reflecting whole screened populations. Large-scale testing in real conditions is required to assess the feasibility of integrating those algorithms in clinical settings.

Telecytologic diagnosis of cervical smears for triage of self-sampled human papillomavirus-positive women in a resource-limited setting: concept development before implementation.

INTRODUCTION: Cytology is an option for triaging human papillomavirus (HPV)-positive women. The interpretation of cytologic slides requires expertise and financial resources that are not always available in resource-limited settings. A solution could be offered by manual preparation and digitization of slides on site for real-time remote cytologic diagnosis by specialists. In the present study, we evaluated the operational feasibility and cost of manual preparation and digitization of thin-layer slides and the diagnostic accuracy of screening with virtual microscopy. MATERIALS AND METHODS: Operational feasibility was evaluated on 30 cervical samples obtained during colposcopy. The simplicity of the process and cellularity and quality of digitized thin-layer slides were evaluated. The diagnostic accuracy of digital versus glass slides to detect cervical intraepithelial neoplasia grade 2 or worse was assessed using a cohort of 264 HPV-positive Cameroonian women aged 30 to 49 years. The histologic results served as the reference standard. RESULTS: Manual preparation was found to be feasible and economically viable. The quality characteristics of the digital slides were satisfactory, and the mean cellularity was 6078 squamous cells per slide. When using the atypical squamous cells of undetermined significance or worse threshold for positivity, the diagnostic performance of screening digital slides was not significantly different statistically compared with the same set of slides screened using a light microscope (P = 0.26). CONCLUSIONS: We have developed an innovative triage concept for HPV-positive women. A quality-ensured telecytologic diagnosis could be an effective solution in areas with a shortage of specialists, applying a same day "test-triage-treat" approach. Our results warrant further on-site clinical validation in a large prospective screening trial.