Impaired Visual Function in Posterior Vitreous Detachment Assessed With the Active-Learning Quantitative Contrast Sensitivity Function Test.

Introduction: To investigate whether there is visual function impairment in patients with posterior vitreous detachment (PVD) using the active-learning quantitative contrast sensitivity function test. Methods: In this cross-sectional study, contrast sensitivity was measured in eyes with PVD and eyes without PVD using the quantitative contrast sensitivity function algorithm on the Adaptive Sensory Technology platform. Outcomes included the area under the log contrast sensitivity function curve, contrast acuity, and contrast sensitivity thresholds at 1 to 18 cycles per degree (cpd). Snellen visual acuity (VA) was also measured. Mixed-effects multiple linear regression analyses were performed to evaluate the association between the presence of PVD and visual function, controlling for age and lens status. Results: The cohort comprised 232 healthy eyes of 205 participants; of these, 80 eyes of 69 patients had PVD. There was no significant association between VA and PVD presence. However, PVD was significantly associated with decreased contrast sensitivity thresholds at 1.5 cpd (ß, -0.058; P = .003) and 3 cpd (ß, -0.067; P = .004). Contrast sensitivity thresholds at lower (1 cpd) or higher (6, 12, 18 cpd) spatial frequencies did not significantly correlate with PVD presence. Even in the subgroup of symptomatic PVD eyes, VA was not significantly decreased, while quantitative contrast sensitivity function outcomes showed visual function deficits at low spatial frequencies (1.5 cpd and 3 cpd). Conclusions: Contrast sensitivity measured with the quantitative contrast sensitivity function test showed visual function deficits in eyes with PVD that would have been missed with VA testing alone. Incorporating this test in the retina clinic might offer a more comprehensive functional assessment of eyes with PVD, serving as an adjunct outcome metric in clinical decision-making.

Deep learning for enhanced spectral analysis of MA-XRF datasets of paintings.

Recent advancements of noninvasive imaging techniques applied for the study and conservation of paintings have driven a rapid development of cutting-edge computational methods. Macro x-ray fluorescence (MA-XRF), a well-established tool in this domain, generates complex and voluminous datasets that pose analytical challenges. To address this, we have incorporated machine learning strategies specifically designed for the analysis as they allow for identification of nontrivial dependencies and classification within these high-dimensional data, thereby promising comprehensive interrogation. We introduce a deep learning algorithm trained on a synthetic dataset that allows for fast and accurate analysis of the XRF spectra in MA-XRF datasets. This approach successfully overcomes the limitations commonly associated with traditional deconvolution methods. Applying this methodology to a painting by Raphael, we demonstrate that our model not only achieves superior accuracy in quantifying the fluorescence line intensities but also effectively eliminates the artifacts typically observed in elemental maps generated through conventional analysis methods.

Diffusion Correction in Fricke Hydrogel Dosimeters: A Deep Learning Approach with 2D and 3D Physics-Informed Neural Network Models.

In this work an innovative approach was developed to address a significant challenge in the field of radiation dosimetry: the accurate measurement of spatial dose distributions using Fricke gel dosimeters. Hydrogels are widely used in radiation dosimetry due to their ability to simulate the tissue-equivalent properties of human tissue, making them ideal for measuring and mapping radiation dose distributions. Among the various gel dosimeters, Fricke gels exploit the radiation-induced oxidation of ferrous ions to ferric ions and are particularly notable due to their sensitivity. The concentration of ferric ions can be measured using various techniques, including magnetic resonance imaging (MRI) or spectrophotometry. While Fricke gels offer several advantages, a significant hurdle to their widespread application is the diffusion of ferric ions within the gel matrix. This phenomenon leads to a blurring of the dose distribution over time, compromising the accuracy of dose measurements. To mitigate the issue of ferric ion diffusion, researchers have explored various strategies such as the incorporation of additives or modification of the gel composition to either reduce the mobility of ferric ions or stabilize the gel matrix. The computational method proposed leverages the power of artificial intelligence, particularly deep learning, to mitigate the effects of ferric ion diffusion that can compromise measurement precision. By employing Physics Informed Neural Networks (PINNs), the method introduces a novel way to apply physical laws directly within the learning process, optimizing the network to adhere to the principles governing ion diffusion. This is particularly advantageous for solving the partial differential equations that describe the diffusion process in 2D and 3D. By inputting the spatial distribution of ferric ions at a given time, along with boundary conditions and the diffusion coefficient, the model can backtrack to accurately reconstruct the original ion distribution. This capability is crucial for enhancing the fidelity of 3D spatial dose measurements, ensuring that the data reflect the true dose distribution without the artifacts introduced by ion migration. Here, multidimensional models able to handle 2D and 3D data were developed and tested against dose distributions numerically evolved in time from 20 to 100 h. The results in terms of various metrics show a significant agreement in both 2D and 3D dose distributions. In particular, the mean square error of the prediction spans the range 1×10-6-1×10-4, while the gamma analysis results in a 90-100% passing rate with 3%/2 mm, depending on the elapsed time, the type of distribution modeled and the dimensionality. This method could expand the applicability of Fricke gel dosimeters to a wider range of measurement tasks, from simple planar dose assessments to intricate volumetric analyses. The proposed technique holds great promise for overcoming the limitations imposed by ion diffusion in Fricke gel dosimeters.

The Ergonomic Evaluation of Attendings and Trainees Across the Vitreoretinal Service as Measured by a Wearable Device.

BACKGROUND AND OBJECTIVE: A cross-sectional prospective study to examine ergonomic differences in vitreoretinal settings: surgery, clinic, and dedicated procedure clinic. PATIENTS AND METHODS: Three vitreoretinal surgeons, three fellows, and one resident at a tertiary eye care facility. Participants wore an Upright Go 2 posture device and posture was recorded in each setting between July 1 to August 31, 2023. RESULTS: Time in upright and poor postures was tracked. Significant differences were found in postural score for attendings between work settings (P < 0.01). Trainees showed no significant difference between settings. Poor posture in surgery was linked to microscope use and scleral buckle placement; in the clinic, it was associated with pan-retinal photocoagulation and injection minutes; in procedure clinic, it was ophthalmologist-dependent and those performing injections. CONCLUSIONS: Ergonomic considerations are crucial in vitreoretinal practice. Attendings and trainees should focus on posture in surgery and clinic settings to enhance career longevity. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

A review of diamond dosimeters in advanced radiotherapy techniques.

This review article synthesizes key findings from studies on the use of diamond dosimeters in advanced radiotherapy techniques, showcasing their applications, challenges, and contributions to enhancing dosimetric accuracy. The article explores various dosimeters, highlighting synthetic diamond dosimeters as potential candidates especially due to their high spatial resolution and negligible ion recombination effect. The clinically validated commercial dosimeter, PTW microDiamond (mD), faces limitations in small fields, proton and hadron therapy and ultra-high dose per pulse (UHDPP) conditions. Variability in reported values for field sizes < $<$ 2 × $\times$ 2 cm 2 ${\rm cm}^2$ is noted, reflecting the competition between volume averaging and density perturbation effects. PTW's introduction of flashDiamond (fD) holds promise for dosimetric measurements in UHDPP conditions and is reliable for commissioning ultra-high dose rate (UHDR) electron beam systems, pending the clinical validation of the device. Other advancements in diamond detectors, such as in 3D configurations and real-time dose per pulse x-ray detectors, are considered valuable in overcoming challenges posed by modern radiotherapy techniques, alongside relative dosimetry and pre-treatment verifications. The studies discussed collectively provide a comprehensive overview of the evolving landscape of diamond dosimetry in the field of radiotherapy, and offer insights into future directions for research and development in the field.

Ten-Year Follow-Up of Fellow Eyes in Patients with Unilateral Naïve Exudative AMD.

PURPOSE: To determine the 10-year morphological outcomes and identify potential risk factors for exudative AMD in the fellow eyes (FE) in patients with naïve exudative AMD. METHODS: Data from 100 patients were retrospectively reviewed. Baseline macular neovascularization (MNV) type in the exudative AMD eye and presence of drusen, intraretinal hyperreflective foci (iHRF), non-foveal incomplete atrophy (iRORA), central retinal thickness and subfoveal choroidal thickness in the FEs were analyzed as biomarkers for progression in the second eye. RESULTS: 54 patients developed exudative AMD in the FE at the end of the follow-up. Subjects with type 2 and 3 MNV in the exudative AMD eye had a higher risk of exudative AMD in the FE (HR=3.365; p=0.039 and HR=3.801; p=0.037). FEs with drusen (large HR=6.938, p=0.001; cuticular HR=6.937, p<0.0001; subretinal drusenoid deposits HR=13.678, p<0.0001) and iHRF (HR=1.853, p=0.041) were also at higher risk. Seven patients were legally blind by the end of the follow-up. CONCLUSIONS: The rate of exudative AMD in the FE was 54% 10 years after the diagnosis in the exudative eye. The FE of patients with type 2 and 3 MNV was at high risk for early progression. Drusen and iHRF were also significant risk factors for MNV development.

Full-Thickness Macular Hole in a Pediatric Patient With Normal Vision.

A 17-year-old boy presented with a full-thickness macular hole, with 20/20 vision with eccentric fixation in the left eye. Examination of the left eye showed a large macular hole with a base diameter measuring 1,680 µm and temporal macular and mid-peripheral retinal atrophy on ultra-high-definition optical coherence tomography (OCT) scans. Microperimetry showed eccentric fixation with good nasal sensitivity. A 12 x 12-mm extended-field swept-source OCT angiogram showed flow loss in the temporal macula, with slight reduction noted in the choriocapillaris. Given excellent visual acuity, good tolerance by the patient, and large atrophic hole, the decision was made for observation rather than surgery. [Ophthalmic Surg Lasers Imaging Retina 2024;55:607-612.].

Corneal Sensitivity and Neuropathy in Patients With Ocular Graft-Versus-Host Disease.

PURPOSE: To assess corneal sensitivity changes in patients with ocular graft-versus-host disease using a non-contact and Cochet-Bonnet esthesiometer. In addition, we evaluate the association between corneal sensitivity and subbasal nerve changes and epitheliopathy in these patients. METHODS: In this retrospective study, the clinical data and images were evaluated for 36 patients (19 female, 17 male) who fulfilled the inclusion criteria. The analyzed data included demographic and ocular surface parameters, including best-corrected visual acuity, corneal sensitivity with non-contact (mbar) and Cochet-Bonnet (cm) esthesiometer, corneal fluorescein staining (CFS) and symptoms scores, tear volume (Schirmer-I test, mm/5'), and subbasal nerve density (µm/mm2; assessed with in vivo confocal microscopy). RESULTS: The mean age of the study cohort was 59.9 ± 10.5 years. The mean corneal sensitivity assessed by Cochet-Bonnet and non-contact esthesiometer was 5.9 ± 0.3 cm and 7.3 ± 2.0 mbar, respectively. The ocular surface parameters included a corneal fluorescein staining (CFS) score, as per the National Eye Institute grading scheme, of 6.9 ± 3.5, and a Schirmer-I test result of 7.5 ± 6.2 mm/5 minutes.. Total corneal subbasal nerve density was inversely associated with CFS scores (r = -0.74; P < 0.001). Moreover, similar correlations between CFS scores and main trunk (r = -0.62; P < 0.001) and branch (r = -0.59; P < 0.001) nerve densities were observed. A significant correlation was found between reduced corneal sensitivity and higher CFS scores (r = 0.66; P < 0.001). Higher pressures were correlated with lower total (r = -0.83; P < 0.001), main trunk (r = -0.62; P < 0.001), and branch (r = -0.72; P < 0.001) nerve densities. The univariate analysis showed that corneal sensitivity loss (assessed with non-contact esthesiometer) was correlated with advanced age of the patients (P = 0.049) and inversely associated with total (P < 0.001), main trunk (P < 0.001), and branch (P < 0.001) nerve densities. In addition, sensitivity loss was inversely associated with punctal occlusion (cauterization (P = 0.001) or plug placement (P < 0.001). The multivariate analysis adjusted for age and punctal occlusion confirmed the associations in the univariate analysis. CONCLUSIONS: In this study, we observed that corneal sensitivity loss was associated with reduced main trunk, branch, and total nerve density in patients with ocular graft-versus-host disease. In addition, a significant correlation was observed between reduced corneal nerve density, corneal sensitivity, and severity of epitheliopathy.

Data-Driven Identification of Stroke through Machine Learning Applied to Complexity Metrics in Multimodal Electromyography and Kinematics.

A stroke represents a significant medical condition characterized by the sudden interruption of blood flow to the brain, leading to cellular damage or death. The impact of stroke on individuals can vary from mild impairments to severe disability. Treatment for stroke often focuses on gait rehabilitation. Notably, assessing muscle activation and kinematics patterns using electromyography (EMG) and stereophotogrammetry, respectively, during walking can provide information regarding pathological gait conditions. The concurrent measurement of EMG and kinematics can help in understanding disfunction in the contribution of specific muscles to different phases of gait. To this aim, complexity metrics (e.g., sample entropy; approximate entropy; spectral entropy) applied to EMG and kinematics have been demonstrated to be effective in identifying abnormal conditions. Moreover, the conditional entropy between EMG and kinematics can identify the relationship between gait data and muscle activation patterns. This study aims to utilize several machine learning classifiers to distinguish individuals with stroke from healthy controls based on kinematics and EMG complexity measures. The cubic support vector machine applied to EMG metrics delivered the best classification results reaching 99.85% of accuracy. This method could assist clinicians in monitoring the recovery of motor impairments for stroke patients.

Longitudinal Assessment of Intraretinal Microvascular Abnormalities in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: To longitudinally investigate the changes in intraretinal microvascular abnormalities (IRMAs) over time, employing swept-source optical coherence tomography angiography in eyes with diabetic retinopathy. Methods: In this retrospective, longitudinal study, we evaluated 12 × 12-mm swept-source optical coherence tomography angiography centered on the macula at baseline and last available follow-up visit for (1) IRMA changes during follow-up, defined as (a) stable, (b) regressed, (c) obliterated, and (d) progressed; and the (2) development of new neovascularization (NV) and their origins. Competing-risk survival analysis was used to assess the factors associated with these changes. Results: In total, 195 eyes from 131 participants with diabetic retinopathy were included. Stable, regressed, obliterated, and progressed IRMA were observed in 65.1%, 12.8%, 11.3%, and 19% of eyes with diabetic retinopathy, respectively. Anti-VEGF injections during the follow-up periods and a slower increase of foveal avascular zone were associated with IRMA regression (P < 0.001 and P = 0.039). Obliterated IRMA were correlated with previous panretinal photocoagulation (P < 0.001) and a lower deep capillary plexus vessel density at baseline (P = 0.007), as well as with follow-up anti-VEGF injections (P = 0.025). A higher baseline ischemia index (ISI) and panretinal photocoagulation during the follow-up periods were associated with IRMA progression (P = 0.049 and P < 0.001). A faster increase in ISI predicted the development of NV elsewhere (NVE) from veins (P < 0.001). No significant factors were found to be associated with NVE originating from IRMA. Conclusions: Changes in IRMA closely correlated with the severity of retinal ischemia and treatment. Notably, our study confirmed the potential, yet relatively rare, development of NVE from IRMA in a large cohort; however, the risk factors associated with this transformation require further exploration.

Effects of Kinematic Hardening of Mucus Polymers in an Airway Closure Model.

The formation of a liquid plug inside a human airway, known as airway closure, is computationally studied by considering the elastoviscoplastic (EVP) properties of the pulmonary mucus covering the airway walls for a range of liquid film thicknesses and Laplace numbers. The airway is modeled as a rigid tube lined with a single layer of an EVP liquid. The Saramito-Herschel-Bulkley (Saramito-HB) model is coupled with an Isotropic Kinematic Hardening model (Saramito-HB-IKH) to allow energy dissipation at low strain rates. The rheological model is fitted to the experimental data under healthy and cystic fibrosis (CF) conditions. Yielded/unyielded regions and stresses on the airway wall are examined throughout the closure process. Yielding is found to begin near the closure in the Saramito-HB model, whereas it occurs noticeably earlier in the Saramito-HB-IKH model. The kinematic hardening is seen to have a notable effect on the closure time, especially for the CF case, with the effect being more pronounced at low Laplace numbers and initial film thicknesses. Finally, standalone effects of rheological properties on wall stresses are examined considering their physiological values as baseline.

Progressive Choriocapillaris Changes on Optical Coherence Tomography Angiography Correlate With Stage Progression in AMD.

Purpose: We investigated the association between inner choroid flow deficit percentage (IC-FD%) using swept-source optical coherence tomography angiography (SS-OCTA) and progression of AMD. Methods: Retrospective, observational study including 64 eyes (42 participants) with early or intermediate AMD at baseline. Participants had two or more consecutive swept-source optical coherence tomography angiography covering a period of at least 18 months. Demographics, visual acuity, and AMD staging based on Beckman classification were reviewed. OCT was analyzed for hyperreflective foci, subretinal drusenoid deposits, hyporeflective drusen cores, and subfoveal choroidal thickness. IC-FD% was measured within the central 3- and 6-mm using a 16-µm slab, after compensation and binarization (Phansalkar method). Mixed-effects Cox regression models assessed the association between imaging biomarkers and AMD progression. Results: During follow-up (37 ± 9 months), 4 eyes with early AMD (31%) progressed to intermediate AMD and 30 (59%) eyes with intermediate AMD developed late AMD (19 geographic atrophy; 11 wet AMD). Baseline hyporeflective drusen core was associated with geographic atrophy development (P < 0.01), whereas greater IC-FD% (3-mm) was associated with wet AMD (P = 0.03). Time-varying analysis showed that faster subfoveal choroidal thickness reduction and IC-FD% (6-mm) increase were associated with geographic atrophy onset (P < 0.05), whereas IC-FD% (3-mm) increase was associated with wet AMD (P = 0.03). Notably, greater IC-FD% increases in the 3 mm (area under the curve = 0.72) and 6 mm (area under the curve = 0.89) were better predictive of wet AMD and geographic atrophy development, respectively. Conclusions: Our longitudinal IC-FD% assessment emphasizes the role of progressive choriocapillaris changes as a biomarker for AMD progression. Our findings support that widespread choriocapillaris alterations (6 mm) may precede progression to geographic atrophy, whereas more central choriocapillaris loss (3 mm) may provide an ischemic stimulus for wet AMD.

In Vivo Correlation Between Macular Pigment Optical Volume and Retinal Layers Thickness.

Purpose: This study aims to investigate the potential in vivo relationship between macular pigment (MP) and retinal layers thickness in healthy subjects and dry, non-advanced age-related macular degeneration (AMD). Methods: An observational, cross-sectional study was conducted. Healthy subjects >40 years and patients with early or intermediate AMD were recruited. Structural OCT and macular pigment optical volume (MPOV) were collected for each subject. Retinal layers parameters were calculated based on the standard early treatment diabetic retinopathy study (ETDRS) map. Additionally, MPOV within 1°, 2°, and 9° of eccentricity was assessed and associated with retinal layers thickness and volume. Linear mixed-effects models were used to test the relationship between MP and structural OCT parameters, while adjusting for known possible confounding factors. Results: A total of 144 eyes of 91 subjects (60.4% females) were evaluated, comprising 43% normal eyes and 57% with early/intermediate AMD. Among the retinal layers, only the outer nuclear layer (ONL) thickness and volume appeared to be associated to higher MP levels. Specifically, the central ONL thickness was identified as a significant predictor of the MPOV 1°(P = 0.04), while the parafoveal ONL thickness (inner ETDRS subfield) was identified as a significant fixed effect on the MPOV 9° (P = 0.037). Age and the presence of drusen or subretinal drusenoid deposits were also tested without showing significant correlations. Conclusions: Among the retinal layers examined, only the ONL thickness demonstrated a significant association with MPOV. Consequently, ONL thickness might serve as a potential biomarker related to MP levels.

Decreased Macular Choriocapillaris Perfusion Correlates with Contrast Sensitivity Function in Dry Age-Related Macular Degeneration.

PURPOSE: To investigate the relationships between contrast sensitivity (CS), choriocapillaris perfusion, and other structural OCT biomarkers in dry age-related macular degeneration (AMD). DESIGN: Cross-sectional, observational study. PARTICIPANTS: One hundred AMD eyes (22 early, 52 intermediate, and 26 late) from 74 patients and 45 control eyes from 37 age-similar subjects. METHODS: All participants had visual acuity (VA) assessment, quantitative CS function (qCSF) testing, macular OCT, and 6 × 6-mm swept-source OCT angiography scans on the same day. OCT volumes were analyzed for subretinal drusenoid deposits and hyporeflective drusen cores, and to measure thickness of the outer nuclear layer. OCT angiography scans were utilized to calculate drusen volume and inner choroid flow deficit percentage (IC-FD%), and to measure the area of choroidal hypertransmission defects (HTDs). Inner choroid flow deficit percentage was measured from a 16-µm thick choriocapillaris slab after compensation and binarization with Phansalkar's method. Generalized linear mixed-effects models were used to evaluate the associations between functional and structural variables. MAIN OUTCOME MEASURES: To explore the associations between qCSF-measured CS, IC-FD%, and various AMD imaging biomarkers. RESULTS: Age-related macular degeneration exhibited significantly reduced qCSF metrics eyes across all stages compared with controls. Univariate analysis revealed significant associations between various imaging biomarkers, reduced qCSF metrics, and VA in both groups. Multivariate analysis confirmed that higher IC-FD% in the central 5 mm was significantly associated with decreases in all qCSF metrics in AMD eyes (ß = -0.74 to -0.25, all P < 0.05), but not with VA (P > 0.05). Outer nuclear layer thickness in the central 3 mm correlated with both VA (ß = 2.85, P < 0.001) and several qCSF metrics (ß = 0.01-0.90, all P < 0.05), especially in AMD eyes. Further, larger HTD areas were associated with decreased VA (ß = -0.89, P < 0.001) and reduced CS at low-intermediate frequencies across AMD stages (ß = -0.30 to -0.29, P < 0.001). CONCLUSIONS: The significant association between IC-FD% in the central 5 mm and qCSF-measured CS reinforces the hypothesis that decreased macular choriocapillaris perfusion contributes to visual function changes in AMD, which are more pronounced in CS than in VA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Advanced neuroimaging techniques to explore the effects of motor and cognitive rehabilitation in multiple sclerosis.

INTRODUCTION: Progress in magnetic resonance imaging (MRI) technology and analyses is improving our comprehension of multiple sclerosis (MS) pathophysiology. These advancements, which enable the evaluation of atrophy, microstructural tissue abnormalities, and functional plasticity, are broadening our insights into the effectiveness and working mechanisms of motor and cognitive rehabilitative treatments. AREAS COVERED: This narrative review with selected studies discusses findings derived from the application of advanced MRI techniques to evaluate structural and functional neuroplasticity modifications underlying the effects of motor and cognitive rehabilitative treatments in people with MS (PwMS). Current applications as outcome measure in longitudinal trials and observational studies, their interpretation and possible pitfalls and limitations in their use are covered. Finally, we examine how the use of these techniques could evolve in the future to improve monitoring of motor and cognitive rehabilitative treatments. EXPERT COMMENTARY: Despite substantial variability in study design and participant characteristics in rehabilitative studies for PwMS, improvements in motor and cognitive functions accompanied by structural and functional brain modifications induced by rehabilitation can be observed. However, significant enhancements to refine rehabilitation strategies are needed. Future studies in this field should strive to implement standardized methodologies regarding MRI acquisition and processing, possibly integrating multimodal measures. This will help identifying relevant markers of treatment response in PwMS, thus improving the use of rehabilitative interventions at individual level. The combination of motor and cognitive strategies, longer periods of treatment, as well as adequate follow-up assessments will contribute to enhance the quality of evidence in support of their routine use.

Comprehensive dosimetric characterization of novel silicon carbide detectors with UHDR electron beams for FLASH radiotherapy.

BACKGROUND: The extremely fast delivery of doses with ultra high dose rate (UHDR) beams necessitates the investigation of novel approaches for real-time dosimetry and beam monitoring. This aspect is fundamental in the perspective of the clinical application of FLASH radiotherapy (FLASH-RT), as conventional dosimeters tend to saturate at such extreme dose rates. PURPOSE: This study aims to experimentally characterize newly developed silicon carbide (SiC) detectors of various active volumes at UHDRs and systematically assesses their response to establish their suitability for dosimetry in FLASH-RT. METHODS: SiC PiN junction detectors, recently realized and provided by STLab company, with different active areas (ranging from 4.5 to 10 mm2) and thicknesses (10-20 µm), were irradiated using 9 MeV UHDR pulsed electron beams accelerated by the ElectronFLASH linac at the Centro Pisano for FLASH Radiotherapy (CPFR). The linearity of the SiC response as a function of the delivered dose per pulse (DPP), which in turn corresponds to a specific instantaneous dose rate, was studied under various experimental conditions by measuring the produced charge within the SiC active layer with an electrometer. Due to the extremely high peak currents, an external customized electronic RC circuit was built and used in conjunction with the electrometer to avoid saturation. RESULTS: The study revealed a linear response for the different SiC detectors employed up to 21 Gy/pulse for SiC detectors with 4.5 mm2/10 µm active area and thickness. These values correspond to a maximum instantaneous dose rate of 5.5 MGy/s and are indicative of the maximum achievable monitored DPP and instantaneous dose rate of the linac used during the measurements. CONCLUSIONS: The results clearly demonstrate that the developed devices exhibit a dose-rate independent response even under extreme instantaneous dose rates and dose per pulse values. A systematic study of the SiC response was also performed as a function of the applied voltage bias, demonstrating the reliability of these dosimeters with UHDR also without any applied voltage. This demonstrates the great potential of SiC detectors for accurate dosimetry in the context of FLASH-RT.

Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial.

BACKGROUND: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings. METHODS: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task). RESULTS: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula. CONCLUSIONS: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements. TRIAL REGISTRATION NUMBER: NCT03679468.

Structural and functional correlates of disability, motor and cognitive performances in multiple sclerosis: Focus on the globus pallidus.

OBJECTIVES: To explore structural and functional alterations of external (GPe) and internal (GPi) globus pallidus in people with multiple sclerosis (pwMS) compared to healthy controls (HC) and analyze their relationship with measures of clinical disability, motor and cognitive impairment. METHODS: Sixty pwMS and 30 HC comparable for age and sex underwent 3.0T MRI, including conventional, diffusion tensor MRI and resting state (RS) functional MRI. Expanded Disability Status Scale (EDSS) scores were rated and timed 25-foot walk (T25FW) test, nine-hole peg test (9HPT), and paced auditory serial addition test (PASAT) were administered. Two operators segmented the GP into GPe and GPi. Volumes, T1/T2 ratio, diffusivity indices and seed-based RS functional connectivity (FC) of the GP and its components were assessed. RESULTS: PwMS had no atrophy or altered diffusivity measures of the GP. Compared to HC, pwMS had higher T1/T2 ratio in both GP regions, which correlated with EDSS score (r = 0.26-0.39, p = 0.01-0.05). RS FC analysis highlighted component-specific functional alterations in pwMS: the GPe had decreased RS FC with fronto-parietal cortices, whereas the GPi had decreased intra-GP RS FC and increased RS FC with the thalamus. Worse EDSS, 9HPT, T25FW and PASAT scores were associated with GP RS FC modifications (r=-0.51‒0.51, p < 0.001). CONCLUSIONS: Structural GP involvement in MS was homogeneous across its portions. Increased T1/T2 ratio values, possibly representing iron accumulation, were related to more severe disability. RS FC alterations of the GPe and GPi were consistent with their roles within the basal ganglia network and correlated with worse functional status, suggesting less efficient communication between structures.

Artificial Intelligence (AI) for Early Diagnosis of Retinal Diseases.

Artificial intelligence (AI) has emerged as a transformative tool in the field of ophthalmology, revolutionizing disease diagnosis and management. This paper provides a comprehensive overview of AI applications in various retinal diseases, highlighting its potential to enhance screening efficiency, facilitate early diagnosis, and improve patient outcomes. Herein, we elucidate the fundamental concepts of AI, including machine learning (ML) and deep learning (DL), and their application in ophthalmology, underscoring the significance of AI-driven solutions in addressing the complexity and variability of retinal diseases. Furthermore, we delve into the specific applications of AI in retinal diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), Macular Neovascularization, retinopathy of prematurity (ROP), retinal vein occlusion (RVO), hypertensive retinopathy (HR), Retinitis Pigmentosa, Stargardt disease, best vitelliform macular dystrophy, and sickle cell retinopathy. We focus on the current landscape of AI technologies, including various AI models, their performance metrics, and clinical implications. Furthermore, we aim to address challenges and pitfalls associated with the integration of AI in clinical practice, including the "black box phenomenon", biases in data representation, and limitations in comprehensive patient assessment. In conclusion, this review emphasizes the collaborative role of AI alongside healthcare professionals, advocating for a synergistic approach to healthcare delivery. It highlights the importance of leveraging AI to augment, rather than replace, human expertise, thereby maximizing its potential to revolutionize healthcare delivery, mitigate healthcare disparities, and improve patient outcomes in the evolving landscape of medicine.