Enhancing intraoperative tumor delineation with multispectral short-wave infrared fluorescence imaging and machine learning

SIGNIFICANCE: Fluorescence-guided surgery (FGS) provides specific real-time visualization of tumors, but intensity-based measurement of fluorescence is prone to errors. Multispectral imaging (MSI) in the short-wave infrared (SWIR) has the potential to improve tumor delineation by enabling machine-learning classification of pixels based on their spectral characteristics. AIM: Determine whether MSI can be applied to FGS and combined with machine learning to provide a robust method for tumor visualization. APPROACH: A multispectral SWIR fluorescence imaging device capable of collecting data from six spectral filters was constructed and deployed on neuroblastoma (NB) subcutaneous xenografts ( n = 6 ) after the injection of a NB-specific NIR-I fluorescent probe (Dinutuximab-IRDye800). We constructed image cubes representing fluorescence collected from ∼ 850 to 1450 nm and compared the performance of seven learning-based methods for pixel-by-pixel classification, including linear discriminant analysis, k -nearest neighbor classification, and a neural network. RESULTS: The spectra of tumor and non-tumor tissue were subtly different and conserved between individuals. In classification, a combine principal component analysis and k -nearest-neighbor approach with area under curve normalization performed best, achieving 97.5% per-pixel classification accuracy (97.1%, 93.5%, and 99.2% for tumor, non-tumor tissue and background, respectively). CONCLUSIONS: The development of dozens of new imaging agents provides a timely opportunity for multispectral SWIR imaging to revolutionize next-generation FGS

A roadmap for the clinical implementation of optical-imaging biomarkers

Clinical workflows for the non-invasive detection and characterization of disease states could benefit from optical-imaging biomarkers. In this Perspective, we discuss opportunities and challenges towards the clinical implementation of optical-imaging biomarkers for the early detection of cancer by analysing two case studies: the assessment of skin lesions in primary care, and the surveillance of patients with Barrett’s oesophagus in specialist care. We stress the importance of technical and biological validations and clinical-utility assessments, and the need to address implementation bottlenecks. In addition, we define a translational roadmap for the widespread clinical implementation of optical imaging-technologies

Targeted Multispectral Filter Array Design for Endoscopic Cancer Detection in the Gastrointestinal Tract

Colour differences between healthy and diseased tissue in the gastrointestinal tract are detected visually by clinicians during white light endoscopy (WLE); however, the earliest signs of disease are often just a slightly different shade of pink compared to healthy tissue. Here, we propose to target alternative colours for imaging to improve contrast using custom multispectral filter arrays (MSFAs) that could be deployed in an endoscopic chip-on-tip configuration. Using an open-source toolbox, Opti-MSFA, we examined the optimal design of MSFAs for early cancer detection in the gastrointestinal tract. The toolbox was first extended to use additional classification models (k-Nearest Neighbour, Support Vector Machine, and Spectral Angle Mapper). Using input spectral data from published clinical trials examining the oesophagus and colon, we optimised the design of MSFAs with 3 to 9 different bands. We examined the variation of the spectral and spatial classification accuracy as a function of number of bands. The MSFA designs have high classification accuracies, suggesting that future implementation in endoscopy hardware could potentially enable improved early detection of disease in the gastrointestinal tract during routine screening and surveillance. Optimal MSFA configurations can achieve similar classification accuracies as the full spectral data in an implementation that could be realised in far simpler hardware. The reduced number of spectral bands could enable future deployment of multispectral imaging in an endoscopic chip-on-tip configuration.Comment: 29 page

A clinically translatable hyperspectral endoscopy (HySE) system for imaging the gastrointestinal tract.

Hyperspectral imaging (HSI) enables visualisation of morphological and biochemical information, which could improve disease diagnostic accuracy. Unfortunately, the wide range of image distortions that arise during flexible endoscopy in the clinic have made integration of HSI challenging. To address this challenge, we demonstrate a hyperspectral endoscope (HySE) that simultaneously records intrinsically co-registered hyperspectral and standard-of-care white light images, which allows image distortions to be compensated computationally and an accurate hyperspectral data cube to be reconstructed as the endoscope moves in the lumen. Evaluation of HySE performance shows excellent spatial, spectral and temporal resolution and high colour fidelity. Application of HySE enables: quantification of blood oxygenation levels in tissue mimicking phantoms; differentiation of spectral profiles from normal and pathological ex vivo human tissues; and recording of hyperspectral data under freehand motion within an intact ex vivo pig oesophagus model. HySE therefore shows potential for enabling HSI in clinical endoscopy

Short-wave infrared imaging enables high-contrast fluorescence-guided surgery in neuroblastoma

Fluorescence-guided surgery is set to play a pivotal role in the intraoperative management of pediatric tumors. Short-wave infrared imaging (SWIR) has advantages over conventional near-infrared I (NIR-I) imaging with reduced tissue scattering and autofluorescence. Here, two NIR-I dyes (IRDye800CW and IR12), with long tails emitting in the SWIR range, were conjugated with a clinical-grade anti-GD2 monoclonal antibody (Dinutuximab-beta) to compare NIR-I and SWIR imaging for neuroblastoma surgery. A first-of-its-kind multispectral NIR-I/SWIR fluorescence imaging device was constructed to allow an objective comparison between the two imaging windows. Conjugates were first characterized in vitro. Tissue-mimicking phantoms, imaging specimens of known geometric and material composition, were used to assess the sensitivity and depth penetration of the NIR-I/SWIR device, showing a minimum detectable volume of ~0.9 mm3 and depth penetration up to 3 mm. In vivo, fluorescence imaging using the NIR-I/SWIR device showed a high tumor-to-background ratio (TBR) for both dyes, with anti-GD2-IR800 being significantly brighter than anti-GD2-IR12. Crucially, the system enabled higher TBR at SWIR wavelengths than at NIR-I wavelengths, verifying SWIR imaging enables high-contrast delineation of tumor margins. This work demonstrates that by combining the high-specificity of anti-GD2 antibodies with the availability and translatability of existing NIR-I dyes, along with the advantages of SWIR in terms of depth and tumor signal-to-background ratio, GD2-targeted NIR-I/SWIR-guided surgery could improve the treatment of neuroblastoma patients, warranting investigation in future clinical trials

Fortnightly changes in water transport direction across the mouth of a narrow estuary

This research investigates the dynamics of the axial tidal flow and residual circulation at the lower Guadiana Estuary, south Portugal, a narrow mesotidal estuary with low freshwater inputs. Current data were collected near the deepest part of the channel for 21 months and across the channel during two (spring and neap) tidal cycles. Results indicate that at the deep channel, depth-averaged currents are stronger and longer during the ebb at spring and during the flood at neap, resulting in opposite water transport directions at a fortnightly time scale. The net water transport across the entire channel is up-estuary at spring and down-estuary at neap, i.e., opposite to the one at the deep channel. At spring tide, when the estuary is considered to be well mixed, the observed pattern of circulation (outflow in the deep channel, inflow over the shoals) results from the combination of the Stokes transport and compensating return flow, which varies laterally with the bathymetry. At neap tide (in particular for those of lowest amplitude each month), inflows at the deep channel are consistently associated with the development of gravitational circulation. Comparisons with previous studies suggest that the baroclinic pressure gradient (rather than internal tidal asymmetries) is the main driver of the residual water transport. Our observations also indicate that the flushing out of the water accumulated up-estuary (at spring) may also produce strong unidirectional barotropic outflow across the entire channel around neap tide.info:eu-repo/semantics/publishedVersio