Error mitigation enables PET radiomic cancer characterization on quantum computers.

BACKGROUND: Cancer is a leading cause of death worldwide. While routine diagnosis of cancer is performed mainly with biopsy sampling, it is suboptimal to accurately characterize tumor heterogeneity. Positron emission tomography (PET)-driven radiomic research has demonstrated promising results when predicting clinical endpoints. This study aimed to investigate the added value of quantum machine learning both in simulator and in real quantum computers utilizing error mitigation techniques to predict clinical endpoints in various PET cancer patients. METHODS: Previously published PET radiomics datasets including 11C-MET PET glioma, 68GA-PSMA-11 PET prostate and lung 18F-FDG PET with 3-year survival, low-vs-high Gleason risk and 2-year survival as clinical endpoints respectively were utilized in this study. Redundancy reduction with 0.7, 0.8, and 0.9 Spearman rank thresholds (SRT), followed by selecting 8 and 16 features from all cohorts, was performed, resulting in 18 dataset variants. Quantum advantage was estimated by Geometric Difference (GDQ) score in each dataset variant. Five classic machine learning (CML) and their quantum versions (QML) were trained and tested in simulator environments across the dataset variants. Quantum circuit optimization and error mitigation were performed, followed by training and testing selected QML methods on the 21-qubit IonQ Aria quantum computer. Predictive performances were estimated by test balanced accuracy (BACC) values. RESULTS: On average, QML outperformed CML in simulator environments with 16-features (BACC 70% and 69%, respectively), while with 8-features, CML outperformed QML with + 1%. The highest average QML advantage was + 4%. The GDQ scores were ≤ 1.0 in all the 8-feature cases, while they were > 1.0 when QML outperformed CML in 9 out of 11 cases. The test BACC of selected QML methods and datasets in the IonQ device without error mitigation (EM) were 69.94% BACC, while EM increased test BACC to 75.66% (76.77% in noiseless simulators). CONCLUSIONS: We demonstrated that with error mitigation, quantum advantage can be achieved in real existing quantum computers when predicting clinical endpoints in clinically relevant PET cancer cohorts. Quantum advantage can already be achieved in simulator environments in these cohorts when relying on QML.

Akinetic all-semiconductor programmable swept-source at 1550 nm and 1310 nm with centimeters coherence length.

We demonstrate, for the first time, OCT imaging capabilities of a novel, akinetic (without any form of movement in the tuning mechanism), all-semiconductor, all-electronic tunable, compact and flexible swept source laser technology at 1550 nm and 1310 nm. To investigate its OCT performance, 2D and 3D ex vivo and in vivo OCT imaging was performed at different sweep rates, from 20 kHz up to 200 kHz, with different axial resolutions, about 10 µm to 20 µm, and at different coherence gate displacements, from zero delay to >17 cm. Laser source phase linearity and phase repeatability standard deviation of <2 mrad (<160 pm) were observed without external phase referencing, indicating that the laser operated close to the shot noise limit (~2 × factor); constant percentile wavelengths variations of sliding RIN and ortho RIN <0.2% could be demonstrated, ~5 times better as compared to other swept laser technologies.

Miniature spectrometer and beam splitter for an optical coherence tomography on a silicon chip.

Optical coherence tomography (OCT) has enabled clinical applications that revolutionized in vivo medical diagnostics. Nevertheless, its current limitations owing to cost, size, complexity, and the need for accurate alignment must be overcome by radically novel approaches. Exploiting integrated optics, we assemble the central components of a spectral-domain OCT system on a silicon chip. The spectrometer comprises an arrayed-waveguide grating with 136-nm free spectral range and 0.21-nm wavelength resolution. The beam splitter is realized by a non-uniform adiabatic coupler with its 3-dB splitting ratio being nearly constant over 150 nm. With this device whose overall volume is 0.36 cm(3) we demonstrate high-quality in vivo imaging in human skin with 1.4-mm penetration depth, 7.5-µm axial resolution, and a signal-to-noise ratio of 74 dB. Considering the reasonable performance of this early OCT on-a-chip system and the anticipated improvements in this technology, a completely different range of devices and new fields of applications may become feasible.

Simultaneous dual wavelength eye-tracked ultrahigh resolution retinal and choroidal optical coherence tomography.

We demonstrate an optical coherence tomography device that simultaneously combines different novel ultrabroad bandwidth light sources centered in the 800 and 1060 nm regions, operating at 66 kHz depth scan rate, and a confocal laser scanning ophthalmoscope-based eye tracker to permit motion-artifact-free, ultrahigh resolution and high contrast retinal and choroidal imaging. The two wavelengths of the device provide the complementary information needed for diagnosis of subtle retinal changes, while also increasing visibility of deeper-lying layers to image pathologies that include opaque media in the anterior eye segment or eyes with increased choroidal thickness.

Ultra-Widefield OCT Angiography.

Optical Coherence Tomography Angiography (OCTA), a functional extension of OCT, has the potential to replace most invasive fluorescein angiography (FA) exams in ophthalmology. So far, OCTA's field of view is however still lacking behind fluorescence fundus photography techniques. This is problematic, because many retinal diseases manifest at an early stage by changes of the peripheral retinal capillary network. It is therefore desirable to expand OCTA's field of view to match that of ultra-widefield fundus cameras. We present a custom developed clinical high-speed swept-source OCT (SS-OCT) system operating at an acquisition rate 8-16 times faster than today's state-of-the-art commercially available OCTA devices. Its speed allows us to capture ultra-wide fields of view of up to 90 degrees with an unprecedented sampling density and hence extraordinary resolution by merging two single shot scans with 60 degrees in diameter. To further enhance the visual appearance of the angiograms, we developed for the first time a three-dimensional deep learning based algorithm for denoising volumetric OCTA data sets. We showcase its imaging performance and clinical usability by presenting images of patients suffering from diabetic retinopathy.

Clinical data classification with noisy intermediate scale quantum computers.

Quantum machine learning has experienced significant progress in both software and hardware development in the recent years and has emerged as an applicable area of near-term quantum computers. In this work, we investigate the feasibility of utilizing quantum machine learning (QML) on real clinical datasets. We propose two QML algorithms for data classification on IBM quantum hardware: a quantum distance classifier (qDS) and a simplified quantum-kernel support vector machine (sqKSVM). We utilize these different methods using the linear time quantum data encoding technique ([Formula: see text]) for embedding classical data into quantum states and estimating the inner product on the 15-qubit IBMQ Melbourne quantum computer. We match the predictive performance of our QML approaches with prior QML methods and with their classical counterpart algorithms for three open-access clinical datasets. Our results imply that the qDS in small sample and feature count datasets outperforms kernel-based methods. In contrast, quantum kernel approaches outperform qDS in high sample and feature count datasets. We demonstrate that the [Formula: see text] encoding increases predictive performance with up to + 2% area under the receiver operator characteristics curve across all quantum machine learning approaches, thus, making it ideal for machine learning tasks executed in Noisy Intermediate Scale Quantum computers.

Spectroscopic measurements with dispersion encoded full range frequency domain optical coherence tomography in single- and multilayered non-scattering phantoms.

In this study, depth resolved measurements of absorption profiles in the wavelength range of 800 nm with a bandwidth of 140 nm are demonstrated using high speed spectroscopic frequency domain OCT(SOCT) and a full range reconstruction algorithm (dispersion encoded full range, DEFR). The feasibility of the algorithm for SOCT is tested in simulation and experiment. With proper calibration, SOCT with DEFR is able to extract absolute, depth resolved absorption profiles over the whole wavelength range at once without the need of tuning and performing measurements at single wavelengths sequentially. The superior acquisition speed and better phase stability in frequency domain as compared to time domain results in a better reproducibility and practicability for spectroscopic measurements. In addition, high acquisition speed in excess of 20 kHz allows to measure absorption dynamics with 50 micros time resolution, which might be useful for the investigation of pharmacokinetics or pharmacodynamics. SOCT of approximately 600 microm thick single- and multilayered, weakly scattering phantoms with varying absorption in the range of 5-80 cm(-1), equivalent to blood absorption in capillaries, is presented. SOCT measurements are compared with those using a spectrometer in transmission mode. For Indocyanine Green (ICG), a dynamic absorption measurements are demonstrated.

Patients with active rheumatoid arthritis but only few tender and swollen joints: a subgroup with impaired short term outcome.

The disease activity score of 28 joints (DAS28) is now commonly used for the guidance of treatment decisions in rheumatoid arthritis (RA). The goal of this work was to determine whether patients with DAS28 > 3.2 but less than 2 swollen and 2 tender joints respond differently to treatment than patients with a higher number of active joints. One hundred and ninety two patients with active RA treated in a rheumatology hospital as in-patients were studied prospectively. At admission (T1), release (T2) and 3 months after release (T3) disease activity (DAS28-CRP at T1 + 2, RADAI at T1 + 3), pain (numeric scale at T1 - 3) and function (FFbH at T1 + 3) were measured. A total of 148 patients had two or more (group 1) and 44 less than 2 swollen and tender joints at admission (group 2) but both groups had similar over all DAS28-scores. The groups significantly differed in their outcome after 3 months: group 1 had a significant better reduction of disease activity, pain and functional deficit (p < 0.001 for the fulfilment of defined response criteria and p < 0.05 for comparison of the mean values for pain and function) in comparison to group 2. Although the numbers were small sub-analysis suggested that the differences might be due to a better response to newly administered DMARD and TNF-alpha-inhibitor therapy in group 1. Active RA patients with less than 2 swollen and 2 tender joints represent a subgroup with lower response to treatment with DMARD or TNF-alpha-inhibitors. This has to be taken into account in the management of these patients.

Stimulus-driven versus pilocarpine-induced biometric changes in pseudophakic eyes.

PURPOSE: Most trials that study the lens movement of accommodative intraocular lens (IOLs) use pilocarpine to stimulate ciliary muscle contraction. The aim of this study is to assess in vivo whether a more physiologic, stimulus-driven accommodation is comparable to pilocarpine-induced IOL movement. DESIGN: Controlled patient- and examiner-masked clinical trial. PARTICIPANTS: The study population included 38 eyes with accommodative IOL implants (1CU) and a control group of 28 eyes with conventional open-loop IOLs. METHODS: A high-precision biometry technique, partial coherence interferometry, was used to measure IOL position. Anterior chamber depth was measured during physiologic (near point) and pharmacological (pilocarpine 2%) stimulation. In a subgroup of 14 1CU eyes, IOL position was determined repeatedly within 90 minutes after pilocarpine administration. A different subgroup was investigated as to the effect of cyclopentolate on IOL position. Best-corrected distance visual acuity (VA), best-corrected near VA, and distance-corrected near VA (DCNVA) were assessed using logarithm of the minimum angle of resolution charts. MAIN OUTCOME MEASURES: Anterior chamber depth change under pilocarpine and near-point-driven accommodation. RESULTS: Near-point accommodation did not induce movement of either the accommodating 1CU or the control IOLs. Pilocarpine induced a 201+/-0.137-mm anterior movement of the 1CU IOL (P<0.001), compared with no movement within the control IOL groups (P>0.05). There was no significant (P>0.05) difference in DCNVA between the accommodative and open-loop IOLs. No correlation between near point- or pilocarpine-stimulated IOL movement and DCNVA was found. Concerning the time course of movement after pilocarpine administration, most of the 1CU IOLs showed some movement 30 minutes after application. Cyclopentolate-induced ciliary muscle relaxation caused a posterior IOL movement, as compared with the relaxed state, when focusing on a distant target. CONCLUSION: Pilocarpine-induced ciliary muscle contraction seems to overestimate IOL movement relative to a monocular near-driven stimulus. Therefore, concerning IOL movement, pilocarpine may act as a superstimulus and may not adequately simulate daily life performance of accommodative IOLs. However, it may be helpful to evaluate the maximum potential of an accommodating IOL.

In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid.

For the first time in vivo retinal imaging has been performed with a new compact, low noise Yb-based ASE source operating in the 1 microm range (NP Photonics, lambdac = 1040 nm, Deltalambda = 50 nm, Pout = 30 mW) at the dispersion minimum of water with ~7 microm axial resolution. OCT tomograms acquired at 800 nm are compared to those achieved at 1040 nm showing about 200 microm deeper penetration into the choroid below the retinal pigment epithelium. Retinal OCT at longer wavelengths significantly improves the visualization of the retinal pigment epithelium/choriocapillaris/choroids interface and superficial choroidal layers as well as reduces the scattering through turbid media and therefore might provide a better diagnosis tool for early stages of retinal pathologies such as age related macular degeneration which is accompanied by choroidal neovascularization, i.e., extensive growth of new blood vessels in the choroid and retina.

Measurement of corneal thickness by laser Doppler interferometry.

The laser Doppler interferometry (LDI) technique, which was recently developed for axial eye length measurement, has been modified to measure the corneal thickness of the human eye in vivo. High accuracy is achieved. The standard deviation of the technique is about 7 microns, and improvement by a factor of 5 is possible. First comparisons with a usual slit lamp pachometer show a general agreement but a systematic difference of about 20 microns. Possible reasons for this discrepancy are discussed. Finally, the new method is compared to standard optical and ultrasound pachometry from a theoretical point of view, and advantages and drawbacks of the various techniques are discussed.

Submicrometer precision biometry of the anterior segment of the human eye.

PURPOSE: To demonstrate the feasibility of measuring the anterior structures of the human eye by partial coherence interferometry and to determine its precision for eyes under normal and cycloplegic conditions. METHODS: The dual-beam version of partial coherence interferometry, a recently developed noninvasive optical ranging technique, enables high resolution measurements of several intraocular distances with unprecedented precision. A modified, more sensitive scanning version of this technique was used to assess the central and peripheral corneal thickness, the anterior chamber depth, and the lens thickness of 20 healthy, emmetropic to moderately myopic eyes. Furthermore the anterior structures of three eyes were measured under cycloplegia (1% cyclopentolate) to investigate the influence on the precision of this technique after suppression of residual accommodations. RESULTS: The mean geometric precision (standard deviation) of the measurement of the central corneal thickness was 0.29 micron (range, 0.22 micron to 0.38 micron) and 0.43 micron (range, 0.27 micron to 0.56 micron) for the peripheral corneal thickness at a distance 2 mm from its apex. The precision for measuring the anterior chamber depth and the lens thickness for fixation at infinity was 8.7 microns (range, 3.9 microns to 16.8 microns) and 8.9 microns (rang, 2.9 microns to 14.4 microns) for noncycloplegic eyes and 1.9 microns (range, 1.7 microns to 2 microns) and 1.4 microns (range, 0.7 micron to 1.8 microns) for cycloplegic eyes, respectively. CONCLUSIONS: The dual-beam partial coherence interferometry enables fast, noninvasive, submicrometer precision biometry of the anterior segment of the eye. The precision of determining the anterior chamber depth and the lens thickness is more than one order of magnitude better than that of the currently used ultrasound and optical techniques, and it can be improved by a factor of 5 by using cycloplegia.

Eye elongation during accommodation in humans: differences between emmetropes and myopes.

PURPOSE: The pathophysiology and pathogenesis of myopia are still a matter of controversy. Exaggerated longitudinal eye growth is assumed to play an important role in the development of myopia. A significant correlation between refraction and amount of near-work has been reported. However, current knowledge of changes of axial eye length with accommodation is limited because clinical ultrasound biometry does not provide the precision and resolution required to thoroughly investigate these phenomena. METHODS: Partial coherence interferometry (PCI), a noninvasive biometric technique, uses laser light with short coherence length in combination with interferometry to achieve precision in the micrometer to submicrometer range and resolution of 10 microm. In the present study this technique was used to investigate axial eye length changes in 11 emmetropic and 12 myopic eyes during monocular fixation at the far and near point. In 7 subjects, the contralateral eye has also been measured to investigate interocular differences in eye elongation. RESULTS: All investigated eyes elongated during accommodation. This elongation was more pronounced in emmetropes than in myopes (P < 0.001). Mean accommodation-induced eye elongations of 12.7 microm (range, 8.6-19.2 microm) and 5.2 microm (range, 2.1-9.5 microm), corresponding to a dioptric change of approximately -0.036 D and -0.015 D, were obtained for emmetropes and myopes. No significant difference in accommodative amplitudes between groups (5.1 +/- 1.2 D [range, 3.8-7.1 D] versus 4.1 +/- 2.0 D [range, 1.0-7.1 D]; P = 0.14) was detected. No significant interocular difference in accommodation-induced eye elongation was revealed (P = 0.86). Also, a mean backward movement of the posterior lens pole of 38 microm (range, 9-107 microm) was observed in both study groups. CONCLUSIONS: The detected eye elongation can be explained by the accommodation-induced contraction of the ciliary muscle, which results in forward and inward pulling of the choroid, thus decreasing the circumference of the sclera, and leads to an elongation of the axial eye length. Finally, it was demonstrated that PCI, in contrast to clinical ultrasound, is capable of characterizing eye length changes during accommodation in humans.

Measurement of the axial length of cataract eyes by laser Doppler interferometry.

PURPOSE: To examine the applicability of the recently developed laser Doppler interferometry technique for measuring the axial length of cataract eyes in a realistic clinical situation. To determine the performance of the instrument as a function of cataract grade. To compare the results to those of ultrasound methods. METHODS: A total of 196 cataract eyes of 100 patients were examined. The axial eye length was determined by laser Doppler interferometry and by two different ultrasound techniques, the applanation technique and the immersion technique. The cataract grade was determined by a commercial instrument that measures backscattered light. RESULTS: Laser Doppler interferometry worked very well except in the cases of the highest cataract grades (4% of the eyes of this study were not measurable because of a too-high lens density). Only 3.5% of the other eyes were not measurable because of fixation problems of the patients. The precision of laser Doppler interferometry is not influenced by the cataract grade (except the highest grade). The standard deviation of the geometric eye length is approximately 20 microns. Linear regression analysis revealed a very good correlation of laser Doppler interferometry and ultrasonic measurements, but a systematic difference was found. The eye lengths measured by laser Doppler interferometry were about 0.18 mm longer than those measured by the immersion technique and about 0.47 mm longer than those measured by the applanation technique. CONCLUSION: These differences are attributed to the laser Doppler interferometry results including the retinal thickness and indentation of the cornea by the applanation technique. The main advantages of the laser Doppler interferometry technique are high precision, high accuracy, and more comfort for the patient because it is a noncontact method, anesthesia is unnecessary, and the risk of corneal infection is avoided.

Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography.

The feasibility of spectroscopic optical coherence tomography (SOCT) to quantify spatially localized absorption profiles of chromophores embedded in weakly scattering media with a single measurement over the full spectral bandwidth of the light source was investigated by using a state-of-the-art ultra-broad bandwidth Ti:Al(2)O(3) laser (lambdac = 800 nm, Deltalambda = 260 nm, P(out) = 120 mW ex-fiber). The precision of the method as a function of the chromophore absorption, the sample thickness, and different parameters related to the measurement procedure was evaluated both theoretically and experimentally in single and multilayered phantoms. It is demonstrated that in weakly scattering media SOCT is able to extract mua(lambda) as small as 0.5 mm-1 from 450 mum thick phantoms with a precision of ~2% in the central and ~8% at the edges of the used wavelength region. As expected, in phantoms with the same absorption properties and thickness ~180 mum the precision of SOCT decreases to >10% in the central wavelength region.

Ultrahigh resolution Fourier domain optical coherence tomography.

We present, for the first time, in vivo ultrahigh resolution (~2.5 microm in tissue), high speed (10000 A-scans/second equivalent acquisition rate sustained over 160 A-scans) retinal imaging obtained with Fourier domain (FD) OCT employing a commercially available, compact (500x260mm), broad bandwidth (120 nm at full-width-at-half-maximum centered at 800 nm) Titanium:sapphire laser (Femtosource Integral OCT, Femtolasers Produktions GmbH). Resolution and sampling requirements, dispersion compensation as well as dynamic range for ultrahigh resolution FD OCT are carefully analyzed. In vivo OCT sensitivity performance achieved by ultrahigh resolution FD OCT was similar to that of ultrahigh resolution time domain OCT, although employing only 2-3 times less optical power (~300 microW). Visualization of intra-retinal layers, especially the inner and outer segment of the photoreceptor layer, obtained by FDOCT was comparable to that, accomplished by ultrahigh resolution time domain OCT, despite an at least 40 times higher data acquisition speed of FD OCT.

Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography.

We interfaced color Doppler Fourier domain optical coherence tomography (CD-FDOCT) with a commercial OCT system to perform in vivo studies of human retinal blood flow in real time. FDOCT does not need reference arm scanning and records one full depth and Doppler profile in parallel. The system operates with an equivalent A-scan rate of 25 kHz and allows real time imaging of the color encoded Doppler information together with the tissue morphology at a rate of 2-4 tomograms (40 x 512 pixel) per second. The recording time of a single tomogram (160 x 512 data points) is only 6,4ms. Despite the high detection speed we achieve a system sensitivity of 86dB using a beam power of 500microW at the cornea. The fundus camera allows simultaneous view for selection of the region of interest. We observe bi-directional blood flow and pulsatility of blood velocity in retinal vessels with a Doppler detection bandwidth of 12.5 kHz and a longitudinal velocity sensitivity in tissue of 200microm/s.

Enhanced visualization of choroidal vessels using ultrahigh resolution ophthalmic OCT at 1050 nm.

In this article the ability of ultrahigh resolution ophthalmic optical coherence tomography (OCT) to image small choroidal blood vessels below the highly reflective and absorbing retinal pigment epithelium is demonstrated for the first time. A new light source (lambdac= 1050 nm, Deltalambda = 165 nm, Pout= 10 mW), based on a photonic crystal fiber pumped by a compact, self-starting Ti:Al2O3 laser has therefore been developed. Ex-vivo ultrahigh resolution OCT images of freshly excised pig retinas acquired with this light source demonstrate enhanced penetration into the choroid and better visualization of choroidal vessels as compared to tomograms acquired with a state-of-the art Ti:Al2O3 laser (Femtolasers Compact Pro, lc= 780 nm, Deltalambda= 160 nm, Pout= 400 mW), normally used in clinical studies for in vivo ultrahigh resolution ophthalmic OCT imaging. These results were also compared with retinal tomograms acquired with a novel, spectrally broadened fiber laser (MenloSystems, lambdac= 1350 nm, Deltalambda= 470 nm, Pout = 4 mW) permitting even greater penetration in the choroid. Due to high water absorption at longer wavelengths retinal OCT imaging at ~1300 nm may find applications in animal ophthalmic studies. Detection and follow-up of choroidal neovascularization improves early diagnosis of many retinal pathologies, e.g. age-related macular degeneration or diabetic retinopathy and can aid development of novel therapy approaches.

Interferometric measurement of corneal thickness with micrometer precision.

The recently developed partial coherence laser Doppler interferometry technique was improved to measure central and peripheral corneal thickness with high precision. Corneal thickness profiles were measured on 18 eyes of health, volunteer subjects. All of these eyes were measurable at angles (between visual axis and measuring direction) ranging from 20 degrees nasal to 25 degrees temporal. At larger angles (up to 35 degrees) only part of the eyes was measurable. The thickness profiles of the 18 corneas have a nearly perfectly parabolic shape within the measured region. The precision (standard deviation) was 1.6 microns for central measurements and decreased somewhat to about 3.5 microns at measuring angles in the range of 25 to 30 degrees. No significant interobserver variability was found on 14 eyes measured by three different observers. This study indicates that the new technique is likely to be superior to currently used ultrasound and conventional optical pachymetry techniques, especially for refractive procedures.