Innovative experimental concepts for optical coherence tomography

Optical Coherence Tomography (OCT) is a recent biomedical imaging technique based on low-coherence interferometry that is capable of acquiring depth-resolved reflectivity maps of scattering tissues with high sensitivity. The conventionally employed imaging mode is to build up a cross sectional image by scanning the sample surface with a point illumination. In order to increase imaging speed, the concept of parallel detection has been introduced to OCT. Here, a whole sample line or even surface is imaged directly onto an array of photodetectors, making the lateral scanning motion obsolete. A customized detector array has been developed in our institute for parallel OCT imaging based on complimentary metal-oxide-semiconductor (CMOS) technology. It associates a signal processing circuit to each photosensitive area of the array, capable of demodulating the interferometric signal on-chip. In this manner, only the signal envelop has to be read out, allowing for a high dynamic range and high frame rates. At the beginning of the thesis, this device had only been tested for topographic measurements on reflective surfaces. As a direct continuation of this previous work, the initial objective of this thesis has been to extend its application to parallel OCT in scattering samples and to identify other uses of this technology in the field of OCT. Accordingly, the first part of this work is dedicated to parallel detection in OCT, using this customized CMOS detector array. The feasibility of the approach is shown experimentally on scattering samples. Reflective surfaces covered with scattering solutions of varying concentration and onion samples are studied. Furthermore, the initial goal of fast OCT imaging is pursued by using the detector at its technological limits and realizing video-rate, three-dimensional OCT acquisitions of a dynamically changing sample. The thermal deformations induced by the probing beam on a dark strand of human hair are imaged at 25 volume acquisitions per second. Identified as a possible new application for the CMOS detector array, the concept of wavelength de-multiplexing for spectroscopic OCT is investigated in the second part of this thesis. Wavelength de-multiplexing is an experimental method for realizing spectroscopically resolved, time-domain OCT measurements. In contrast to the currently employed numerical post-processing methods for extracting spectroscopic information, wavelength de-multiplexing relies on optical wavelength separation in the interferometer detection arm and acquisition of independent wavelength channels using a detector array. The method itself is first studied using a laterally translated photodiode for detection, in order to compare it to the conventional spectroscopic OCT approach. The absorption characteristics of a glass filter and a Nd-doped crystal are measured in this manner. Then, associated to the CMOS detector array in a proof-of-principle experiment, the dynamically changing, spatially resolved absorption of a dye mixing process is measured online. The experimental setup used for wavelength de-multiplexing has lead to an innovative technique that is of interest to low coherence interferometry in general. The axial depth scan employed in all time-domain low coherence interferometry setups should ideally introduce a linear change with time of optical path difference between the interferometer's sample and reference arms. However, depending on the scan method used, the path difference variation is only approximatively linear and can even vary randomly from scan to scan. For precise, phase-sensitive and repetitive measurements the scans have to be calibrated. By increasing the coherence length of part of the detected radiation in the detection arm of the interferometer through narrow spectral filtering, a calibration signal is created that permits the precise measurement of the optical path difference variation and thus its calibration without the need for a secondary interferometer. The usefulness of the approach is demonstrated by combining it with a recently published spectral shaping technique for sidelobe suppression in OCT when using non-Gaussian source spectra. In order to be beneficial, such a technique requires highly repetitive measurements that can only be obtained with particularly stable scanning devices or well calibrated ones. In summary, this thesis studies three innovative experimental concepts that aim to improve OCT imaging speed and imaging quality and proposes them as interesting new tools to the OCT community

Poking Holes and Cutting Corners to Achieve Clifford Gates with the Surface Code

The surface code is currently the leading proposal to achieve fault-tolerant quantum computation. Among its strengths are the plethora of known ways in which fault-tolerant Clifford operations can be performed, namely, by deforming the topology of the surface, by the fusion and splitting of codes, and even by braiding engineered Majorana modes using twist defects. Here, we present a unified framework to describe these methods, which can be used to better compare different schemes and to facilitate the design of hybrid schemes. Our unification includes the identification of twist defects with the corners of the planar code. This identification enables us to perform single-qubit Clifford gates by exchanging the corners of the planar code via code deformation. We analyze ways in which different schemes can be combined and propose a new logical encoding. We also show how all of the Clifford gates can be implemented with the planar code, without loss of distance, using code deformations, thus offering an attractive alternative to ancilla-mediated schemes to complete the Clifford group with lattice surgery

Polychromatic guide star: feasibility study

International audienceAdaptive optics at astronomical telescopes aims at correcting in real time the phase corrugations of incoming wavefronts caused by the turbulent atmosphere, as early proposed by Babcock. Measuring the phase errors requires a bright source located within the isoplanatic patch of the program source. The probability that such a reference source exists is a function of the wavelength, of the required image quality (Strehl ratio), of the turbulence optical properties, and of the direction of the observation. It turns out that the sky coverage is disastrously low in particular in the visible wavelength range where, unfortunately, the gain in spatial resolution brought by adaptive optics is the largest. Foy and Labeyrie have proposed to overcome this difficulty by creating an artificial point source in the sky in the direction of the observation relying on the backscattered light due to a laser beam. This laser guide star (hereinafter referred to as LGS) can be bright enough to allow us to accurately measure the wavefront phase errors, except for two modes which are the piston (not relevant in this case) and the tilt. Pilkington has emphasized that the round trip time of the laser beam to the mesosphere, where the LGS is most often formed, is significantly shorter than the typical tilt coherence time; then the inverse-return-of-light principle causes deflections of the outgoing and the ingoing beams to cancel. The apparent direction of the LGS is independent of the tilt. Therefore the tilt cannot be measured only from the LGS. Until now, the way to overcome this difficulty has been to use a natural guide star to sense the tilt. Although the tilt is sensed through the entire telescope pupil, one cannot use a faint source because $APEX 90% of the variance of the phase error is in the tilt. Therefore, correcting the tilt requires a higher accuracy of the measurements than for higher orders of the wavefront. Hence current adaptive optics devices coupled with a LGS face low sky coverage. Several methods have been proposed to get a partial sky coverage for the tilt. The only one providing us with a full sky coverage is the polychromatic LGS (hereafter referred to as PLGS). We present here a progress report of the R&D; program Etoile Laser Polychromatique et Optique Adaptative (ELP-OA) carried out in France to develop the PLGS concept. After a short recall of the principles of the PLGS, we will review the goal of ELP-OA and the steps to get over to bring it into play. We finally shortly described the effort in Europe to develop the LGS

Polychromatic guide star: feasibility study

International audienceAdaptive optics at astronomical telescopes aims at correcting in real time the phase corrugations of incoming wavefronts caused by the turbulent atmosphere, as early proposed by Babcock. Measuring the phase errors requires a bright source located within the isoplanatic patch of the program source. The probability that such a reference source exists is a function of the wavelength, of the required image quality (Strehl ratio), of the turbulence optical properties, and of the direction of the observation. It turns out that the sky coverage is disastrously low in particular in the visible wavelength range where, unfortunately, the gain in spatial resolution brought by adaptive optics is the largest. Foy and Labeyrie have proposed to overcome this difficulty by creating an artificial point source in the sky in the direction of the observation relying on the backscattered light due to a laser beam. This laser guide star (hereinafter referred to as LGS) can be bright enough to allow us to accurately measure the wavefront phase errors, except for two modes which are the piston (not relevant in this case) and the tilt. Pilkington has emphasized that the round trip time of the laser beam to the mesosphere, where the LGS is most often formed, is significantly shorter than the typical tilt coherence time; then the inverse-return-of-light principle causes deflections of the outgoing and the ingoing beams to cancel. The apparent direction of the LGS is independent of the tilt. Therefore the tilt cannot be measured only from the LGS. Until now, the way to overcome this difficulty has been to use a natural guide star to sense the tilt. Although the tilt is sensed through the entire telescope pupil, one cannot use a faint source because $APEX 90% of the variance of the phase error is in the tilt. Therefore, correcting the tilt requires a higher accuracy of the measurements than for higher orders of the wavefront. Hence current adaptive optics devices coupled with a LGS face low sky coverage. Several methods have been proposed to get a partial sky coverage for the tilt. The only one providing us with a full sky coverage is the polychromatic LGS (hereafter referred to as PLGS). We present here a progress report of the R&D; program Etoile Laser Polychromatique et Optique Adaptative (ELP-OA) carried out in France to develop the PLGS concept. After a short recall of the principles of the PLGS, we will review the goal of ELP-OA and the steps to get over to bring it into play. We finally shortly described the effort in Europe to develop the LGS

Benign external hydrocephalus: a review, with emphasis on management

Benign external hydrocephalus in infants, characterized by macrocephaly and typical neuroimaging findings, is considered as a self-limiting condition and is therefore rarely treated. This review concerns all aspects of this condition: etiology, neuroimaging, symptoms and clinical findings, treatment, and outcome, with emphasis on management. The review is based on a systematic search in the Pubmed and Web of Science databases. The search covered various forms of hydrocephalus, extracerebral fluid, and macrocephaly. Studies reporting small children with idiopathic external hydrocephalus were included, mostly focusing on the studies reporting a long-term outcome. A total of 147 studies are included, the majority however with a limited methodological quality. Several theories regarding pathophysiology and various symptoms, signs, and clinical findings underscore the heterogeneity of the condition. Neuroimaging is important in the differentiation between external hydrocephalus and similar conditions. A transient delay of psychomotor development is commonly seen during childhood. A long-term outcome is scarcely reported, and the results are varying. Although most children with external hydrocephalus seem to do well both initially and in the long term, a substantial number of patients show temporary or permanent psychomotor delay. To verify that this truly is a benign condition, we suggest that future research on external hydrocephalus should focus on the long-term effects of surgical treatment as opposed to conservative management

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society