Deep Tissue Sequencing Using Hypodermoscopy and Augmented Intelligence to Analyze Atypical Pigmented Lesions.

BACKGROUND: Over the past decade, new technologies, devices, and methods have been developed to assist in the diagnosis of cutaneous melanocytic lesions. OBJECTIVE: Our objective was to evaluate the performance of an augmented intelligence system in the assessment of atypical pigmented lesions. METHODS: Nine atypical pigmented lesions on 8 patients were evaluated prior to surgical removal. No lesions had received previous treatment other than a diagnostic biopsy. Prior to surgical removal, each lesion was evaluated by an Augmented Intelligence Dermal Imager (AID) and the assessment parameters reviewed in light of the final histopathological diagnosis. RESULTS: The AID was used to evaluate a limited set of atypical pigmented lesions and showed sensitivity and specificity of 82% and 61%, respectively, based on its internal risk assessment algorithms. LIMITATIONS: These cases represent early assessments of the AID in a clinical setting, all prior assessments having been carried out on digital images. The information received from these evaluations requires further validation and analysis to be able to extrapolate its clinical usefulness. CONCLUSION: The AID combines dermoscopy, hypodermoscopy, and a trained augmented algorithm to produce a diffusion map representing the features of each lesion compared to the learned characteristics from a database of known dermoscopy images of lesions with definitive prior diagnosis. The information gathered from the diffusion map might be used to calculate a malignancy risk factor for the lesion compared to known melanoma features. This malignancy risk factor could be helpful in providing information to justify the biopsy of an atypical pigmented lesion.

Resolution- and throughput-enhanced spectroscopy using a high-throughput computational slit.

There exists a fundamental trade-off between the spectral resolution and the efficiency or throughput for all optical spectrometers. The primary factors affecting the spectral resolution and throughput of an optical spectrometer are the size of the entrance aperture and the optical power of the focusing element. So far, the collective optimization of the above mentioned has proven difficult. Here, we introduce the concept of high-throughput computational slits (HTCS), a numerical technique for improving both the effective spectral resolution and efficiency of a spectrometer. The proposed HTCS approach was experimentally validated using an optical spectrometer configured with a 200 µm entrance aperture, test, and a 50 µm entrance aperture control, demonstrating improvements in the spectral resolution of the spectrum by ∼50% over the control spectral resolution and improvements in efficiency of >2 times over the efficiency of the largest entrance aperture used in this Letter, while producing highly accurate spectra.

Bayesian-based aberration correction and numerical diffraction for improved lensfree on-chip microscopy of biological specimens.

Lensfree on-chip microscopy is an emerging imaging technique that can be used to visualize and study biological specimens without the need for imaging lens systems. Important issues that can limit the performance of lensfree on-chip microscopy include interferometric aberrations, acquisition noise, and image reconstruction artifacts. In this study, we introduce a Bayesian-based method for performing aberration correction and numerical diffraction that accounts for all three of these issues to improve the effective numerical aperture (NA) and signal-to-noise ratio (SNR) of the reconstructed microscopic image. The proposed method was experimentally validated using the USAF resolution target as well as real waterborne Anabaena flos-aquae samples, demonstrating improvements in NA by ∼25% over the standard method, and improvements in SNR of 2.8 and 8.2 dB in the reconstructed image when compared to the reconstructed images produced using the standard method and a maximum likelihood estimation method, respectively.

Lens-free spectral light-field fusion microscopy for contrast- and resolution-enhanced imaging of biological specimens.

A lens-free spectral light-field fusion microscopy (LSLFM) system is presented for enabling contrast- and resolution-enhanced imaging of biological specimens. LSLFM consists of a pulsed multispectral lens-free microscope for capturing interferometric light-field encodings at various wavelengths, and Bayesian-based fusion to reconstruct a fused object light-field from the encodings. By fusing unique object detail information captured at different wavelengths, LSLFM can achieve improved resolution, contrast, and signal-to-noise ratio (SNR) over a single-channel lens-free microscopy system. A five-channel LSLFM system was developed and quantitatively evaluated to validate the design. Experimental results demonstrated that the LSLFM system provided SNR improvements of 6-12 dB, as well as a six-fold improvement in the dispersion index (DI), over that achieved using a single-channel, resolution-enhancing lens-free deconvolution microscopy system or its multi-wavelength counterpart. Furthermore, the LSLFM system achieved an increase in numerical aperture (NA) of ∼16% over a single-channel resolution-enhancing lens-free deconvolution microscopy system at the highest resolution wavelength used in the study. Samples of Staurastrum paradoxum, a waterborne algae, and human corneal epithelial cells were imaged using the system to illustrate its potential for enhanced imaging of biological specimens.

Laser Light-field Fusion for Wide-field Lensfree On-chip Phase Contrast Microscopy of Nanoparticles.

Wide-field lensfree on-chip microscopy, which leverages holography principles to capture interferometric light-field encodings without lenses, is an emerging imaging modality with widespread interest given the large field-of-view compared to lens-based techniques. In this study, we introduce the idea of laser light-field fusion for lensfree on-chip phase contrast microscopy for detecting nanoparticles, where interferometric laser light-field encodings acquired using a lensfree, on-chip setup with laser pulsations at different wavelengths are fused to produce marker-free phase contrast images of particles at the nanometer scale. As a proof of concept, we demonstrate, for the first time, a wide-field lensfree on-chip instrument successfully detecting 300 nm particles across a large field-of-view of ~30 mm2 without any specialized or intricate sample preparation, or the use of synthetic aperture- or shift-based techniques.

Numerical Demultiplexing of Color Image Sensor Measurements via Non-linear Random Forest Modeling.

The simultaneous capture of imaging data at multiple wavelengths across the electromagnetic spectrum is highly challenging, requiring complex and costly multispectral image devices. In this study, we investigate the feasibility of simultaneous multispectral imaging using conventional image sensors with color filter arrays via a novel comprehensive framework for numerical demultiplexing of the color image sensor measurements. A numerical forward model characterizing the formation of sensor measurements from light spectra hitting the sensor is constructed based on a comprehensive spectral characterization of the sensor. A numerical demultiplexer is then learned via non-linear random forest modeling based on the forward model. Given the learned numerical demultiplexer, one can then demultiplex simultaneously-acquired measurements made by the color image sensor into reflectance intensities at discrete selectable wavelengths, resulting in a higher resolution reflectance spectrum. Experimental results demonstrate the feasibility of such a method for the purpose of simultaneous multispectral imaging.

Depth profilometry via multiplexed optical high-coherence interferometry.

Depth Profilometry involves the measurement of the depth profile of objects, and has significant potential for various industrial applications that benefit from non-destructive sub-surface profiling such as defect detection, corrosion assessment, and dental assessment to name a few. In this study, we investigate the feasibility of depth profilometry using an Multiplexed Optical High-coherence Interferometry MOHI instrument. The MOHI instrument utilizes the spatial coherence of a laser and the interferometric properties of light to probe the reflectivity as a function of depth of a sample. The axial and lateral resolutions, as well as imaging depth, are decoupled in the MOHI instrument. The MOHI instrument is capable of multiplexing interferometric measurements into 480 one-dimensional interferograms at a location on the sample and is built with axial and lateral resolutions of 40 µm at a maximum imaging depth of 700 µm. Preliminary results, where a piece of sand-blasted aluminum, an NBK7 glass piece, and an optical phantom were successfully probed using the MOHI instrument to produce depth profiles, demonstrate the feasibility of such an instrument for performing depth profilometry.

Feasibility of long-distance heart rate monitoring using transmittance photoplethysmographic imaging (PPGI).

Photoplethysmography (PPG) devices are widely used for monitoring cardiovascular function. However, these devices require skin contact, which restricts their use to at-rest short-term monitoring. Photoplethysmographic imaging (PPGI) has been recently proposed as a non-contact monitoring alternative by measuring blood pulse signals across a spatial region of interest. Existing systems operate in reflectance mode, many of which are limited to short-distance monitoring and are prone to temporal changes in ambient illumination. This paper is the first study to investigate the feasibility of long-distance non-contact cardiovascular monitoring at the supermeter level using transmittance PPGI. For this purpose, a novel PPGI system was designed at the hardware and software level. Temporally coded illumination (TCI) is proposed for ambient correction, and a signal processing pipeline is proposed for PPGI signal extraction. Experimental results show that the processing steps yielded a substantially more pulsatile PPGI signal than the raw acquired signal, resulting in statistically significant increases in correlation to ground-truth PPG in both short- and long-distance monitoring. The results support the hypothesis that long-distance heart rate monitoring is feasible using transmittance PPGI, allowing for new possibilities of monitoring cardiovascular function in a non-contact manner.