Generating Synthetic Light-Adapted Electroretinogram Waveforms Using Artificial Intelligence to Improve Classification of Retinal Conditions in Under-Represented Populations.

Visual electrophysiology is often used clinically to determine the functional changes associated with retinal or neurological conditions. The full-field flash electroretinogram (ERG) assesses the global contribution of the outer and inner retinal layers initiated by the rods and cone pathways depending on the state of retinal adaptation. Within clinical centers, reference normative data are used to compare clinical cases that may be rare or underpowered within a specific demographic. To bolster either the reference dataset or the case dataset, the application of synthetic ERG waveforms may offer benefits to disease classification and case-control studies. In this study and as a proof of concept, artificial intelligence (AI) to generate synthetic signals using generative adversarial networks is deployed to upscale male participants within an ISCEV reference dataset containing 68 participants, with waveforms from the right and left eye. Random forest classifiers further improved classification for sex within the group from a balanced accuracy of 0.72-0.83 with the added synthetic male waveforms. This is the first study to demonstrate the generation of synthetic ERG waveforms to improve machine learning classification modelling with electroretinogram waveforms.

Optimizing neurointerventional procedures: an algorithm for embolization coil detection and automated collimation to enable dose reduction.

Purpose: Monitoring radiation dose and time parameters during radiological interventions is crucial, especially in neurointerventional procedures, such as aneurysm treatment with embolization coils. The algorithm presented detects the presence of these embolization coils in medical images. It establishes a bounding box as a reference for automated collimation, with the primary objective being to enhance the efficiency and safety of neurointerventional procedures by actively optimizing image quality while minimizing patient dose. Methods: Two distinct methodologies are evaluated in our study. The first involves deep learning, employing the Faster R-CNN model with a ResNet-50 FPN as a backbone and a RetinaNet model. The second method utilizes a classical blob detection approach, serving as a benchmark for comparison. Results: We performed a fivefold cross-validation, and our top-performing model achieved mean mAP@75 of 0.84 across all folds on validation data and mean mAP@75 of 0.94 on independent test data. Since we use an upscaled bounding box, achieving 100% overlap between ground truth and prediction is not necessary. To highlight the real-world applications of our algorithm, we conducted a simulation featuring a coil constructed from an alloy wire, effectively showcasing the implementation of automatic collimation. This resulted in a notable reduction in the dose area product, signifying the reduction of stochastic risks for both patients and medical staff by minimizing scatter radiation. Additionally, our algorithm assists in avoiding extreme brightness or darkness in X-ray angiography images during narrow collimation, ultimately streamlining the collimation process for physicians. Conclusion: To our knowledge, this marks the initial attempt at an approach successfully detecting embolization coils, showcasing the extended applications of integrating detection results into the X-ray angiography system. The method we present has the potential for broader application, allowing its extension to detect other medical objects utilized in interventional procedures.

Deep learning based decoding of single local field potential events.

How is information processed in the cerebral cortex? In most cases, recorded brain activity is averaged over many (stimulus) repetitions, which erases the fine-structure of the neural signal. However, the brain is obviously a single-trial processor. Thus, we here demonstrate that an unsupervised machine learning approach can be used to extract meaningful information from electro-physiological recordings on a single-trial basis. We use an auto-encoder network to reduce the dimensions of single local field potential (LFP) events to create interpretable clusters of different neural activity patterns. Strikingly, certain LFP shapes correspond to latency differences in different recording channels. Hence, LFP shapes can be used to determine the direction of information flux in the cerebral cortex. Furthermore, after clustering, we decoded the cluster centroids to reverse-engineer the underlying prototypical LFP event shapes. To evaluate our approach, we applied it to both extra-cellular neural recordings in rodents, and intra-cranial EEG recordings in humans. Finally, we find that single channel LFP event shapes during spontaneous activity sample from the realm of possible stimulus evoked event shapes. A finding which so far has only been demonstrated for multi-channel population coding.

Drugst.One - a plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

An interactive task-based method for the avoidance of metal artifacts in CBCT.

PURPOSE: Intraoperative cone-beam CT imaging enables 3D validation of implant positioning and fracture reduction for orthopedic and trauma surgeries. However, the emergence of metal artifacts, especially in the vicinity of metallic objects, severely degrades the clinical value of the imaging modality. In previous works, metal artifact avoidance (MAA) methods have been shown to reduce metal artifacts by adapting the scanning trajectory. Yet, these methods fail to translate to clinical practice due to remaining methodological constraints and missing workflow integration. METHODS: In this work, we propose a method to compute the spatial distribution and calibrated strengths of expected artifacts for a given tilted circular trajectory. By visualizing this as an overlay changing with the C-Arm's tilt, we enable the clinician to interactively choose an optimal trajectory while factoring in the procedural context and clinical task. We then evaluate this method in a realistic human cadaver study and compare the achieved image quality to acquisitions optimized using global metrics. RESULTS: We assess the effectiveness of the compared methods by evaluation of image quality gradings of depicted pedicle screws. We find that both global metrics as well as the proposed visualization of artifact distribution enable a drastic improvement compared to standard non-tilted scans. Furthermore, the novel interactive visualization yields a significant improvement in subjective image quality compared to the state-of-the-art global metrics. Additionally we show that by formulating an imaging task, the proposed method allows to selectively optimize image quality and avoid artifacts in the region of interest. CONCLUSION: We propose a method to spatially resolve predicted artifacts and provide a calibrated measure for artifact strength grading. This interactive MAA method proved practical and effective in reducing metal artifacts in the conducted cadaver study. We believe this study serves as a crucial step toward clinical application of an MAA system to improve image quality and enhance the clinical validation of implant placement.

Identification of a chaperone-code responsible for Rad51-mediated genome repair.

Posttranslational modifications of Hsp90 are known to regulate its in vivo chaperone functions. Here, we demonstrate that the lysine acetylation-deacetylation dynamics of Hsp82 is a major determinant in DNA repair mediated by Rad51. We uncover that the deacetylated lysine 27 in Hsp82 dictates the formation of the Hsp82-Aha1-Rad51 complex, which is crucial for client maturation. Intriguingly, Aha1-Rad51 complex formation is not dependent on Hsp82 or its acetylation status; implying that Aha1-Rad51 association precedes the interaction with Hsp82. The DNA damage sensitivity of Hsp82 (K27Q/K27R) mutants are epistatic to the loss of the (de)acetylase hda1Δ; reinforcing the importance of the reversible acetylation of Hsp82 at the K27 position. These findings underscore the significance of the cross talk between a specific Hsp82 chaperone modification code and the cognate cochaperones in a client-specific manner. Given the pivotal role that Rad51 plays during DNA repair in eukaryotes and particularly in cancer cells, targeting the Hda1-Hsp90 axis could be explored as a new therapeutic approach against cancer.

Self-supervised learning for interventional image analytics: toward robust device trackers.

Purpose: The accurate detection and tracking of devices, such as guiding catheters in live X-ray image acquisitions, are essential prerequisites for endovascular cardiac interventions. This information is leveraged for procedural guidance, e.g., directing stent placements. To ensure procedural safety and efficacy, there is a need for high robustness/no failures during tracking. To achieve this, one needs to efficiently tackle challenges, such as device obscuration by the contrast agent or other external devices or wires and changes in the field-of-view or acquisition angle, as well as the continuous movement due to cardiac and respiratory motion. Approach: To overcome the aforementioned challenges, we propose an approach to learn spatio-temporal features from a very large data cohort of over 16 million interventional X-ray frames using self-supervision for image sequence data. Our approach is based on a masked image modeling technique that leverages frame interpolation-based reconstruction to learn fine inter-frame temporal correspondences. The features encoded in the resulting model are fine-tuned downstream in a light-weight model. Results: Our approach achieves state-of-the-art performance, in particular for robustness, compared to ultra optimized reference solutions (that use multi-stage feature fusion or multi-task and flow regularization). The experiments show that our method achieves a 66.31% reduction in the maximum tracking error against the reference solutions (23.20% when flow regularization is used), achieving a success score of 97.95% at a 3× faster inference speed of 42 frames-per-second (on GPU). In addition, we achieve a 20% reduction in the standard deviation of errors, which indicates a much more stable tracking performance. Conclusions: The proposed data-driven approach achieves superior performance, particularly in robustness and speed compared with the frequently used multi-modular approaches for device tracking. The results encourage the use of our approach in various other tasks within interventional image analytics that require effective understanding of spatio-temporal semantics.

Glaucoma detection using non-perfused areas in OCTA.

Multiple ophthalmic diseases lead to decreased capillary perfusion that can be visualized using optical coherence tomography angiography images. To quantify the decrease in perfusion, past studies have often used the vessel density, which is the percentage of vessel pixels in the image. However, this method is often not sensitive enough to detect subtle changes in early pathology. More recent methods are based on quantifying non-perfused or intercapillary areas between the vessels. These methods rely upon the accuracy of vessel segmentation, which is a challenging task and therefore a limiting factor for reliability. Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changing if gaps are present in the segmentation. We present a novel method for distinguishing between glaucoma patients and healthy controls based on features computed from the probability density function of these perfusion-distance areas. The proposed approach is evaluated on different capillary plexuses and outperforms previously proposed methods that use handcrafted features for classification. Moreover the results of the proposed method are in the same range as the ones of convolutional neural networks trained on the raw input images and is therefore a computationally efficient, simple to implement and explainable alternative to deep learning-based approaches.

Oral mucosa - an examination map for confocal laser endomicroscopy within the oral cavity: an experimental clinical study.

OBJECTIVES: Confocal laser endomicroscopy (CLE) is an optical method that enables microscopic visualization of oral mucosa. Previous studies have shown that it is possible to differentiate between physiological and malignant oral mucosa. However, differences in mucosal architecture were not taken into account. The objective was to map the different oral mucosal morphologies and to establish a "CLE map" of physiological mucosa as baseline for further application of this powerful technology. MATERIALS AND METHODS: The CLE database consisted of 27 patients. The following spots were examined: (1) upper lip (intraoral) (2) alveolar ridge (3) lateral tongue (4) floor of the mouth (5) hard palate (6) intercalary line. All sequences were examined by two CLE experts for morphological differences and video quality. RESULTS: Analysis revealed clear differences in image quality and possibility of depicting tissue morphologies between the various localizations of oral mucosa: imaging of the alveolar ridge and hard palate showed visually most discriminative tissue morphology. Labial mucosa was also visualized well using CLE. Here, typical morphological features such as uniform cells with regular intercellular gaps and vessels could be clearly depicted. Image generation and evaluation was particularly difficult in the area of the buccal mucosa, the lateral tongue and the floor of the mouth. CONCLUSION: A physiological "CLE map" for the entire oral cavity could be created for the first time. CLINICAL RELEVANCE: This will make it possible to take into account the existing physiological morphological features when differentiating between normal mucosa and oral squamous cell carcinoma in future work.

Co-ordinate-based positional embedding that captures resolution to enhance transformer's performance in medical image analysis.

Vision transformers (ViTs) have revolutionized computer vision by employing self-attention instead of convolutional neural networks and demonstrated success due to their ability to capture global dependencies and remove spatial biases of locality. In medical imaging, where input data may differ in size and resolution, existing architectures require resampling or resizing during pre-processing, leading to potential spatial resolution loss and information degradation. This study proposes a co-ordinate-based embedding that encodes the geometry of medical images, capturing physical co-ordinate and resolution information without the need for resampling or resizing. The effectiveness of the proposed embedding is demonstrated through experiments with UNETR and SwinUNETR models for infarct segmentation on MRI dataset with AxTrace and AxADC contrasts. The dataset consists of 1142 training, 133 validation and 143 test subjects. Both models with the addition of co-ordinate based positional embedding achieved substantial improvements in mean Dice score by 6.5% and 7.6%. The proposed embedding showcased a statistically significant advantage p-value< 0.0001 over alternative approaches. In conclusion, the proposed co-ordinate-based pixel-wise positional embedding method offers a promising solution for Transformer-based models in medical image analysis. It effectively leverages physical co-ordinate information to enhance performance without compromising spatial resolution and provides a foundation for future advancements in positional embedding techniques for medical applications.

OCTDL: Optical Coherence Tomography Dataset for Image-Based Deep Learning Methods.

Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 2000 OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.

Two-view topogram-based anatomy-guided CT reconstruction for prospective risk minimization.

To facilitate a prospective estimation of the effective dose of an CT scan prior to the actual scanning in order to use sophisticated patient risk minimizing methods, a prospective spatial dose estimation and the known anatomical structures are required. To this end, a CT reconstruction method is required to reconstruct CT volumes from as few projections as possible, i.e. by using the topograms, with anatomical structures as correct as possible. In this work, an optimized CT reconstruction model based on a generative adversarial network (GAN) is proposed. The GAN is trained to reconstruct 3D volumes from an anterior-posterior and a lateral CT projection. To enhance anatomical structures, a pre-trained organ segmentation network and the 3D perceptual loss are applied during the training phase, so that the model can then generate both organ-enhanced CT volume and organ segmentation masks. The proposed method can reconstruct CT volumes with PSNR of 26.49, RMSE of 196.17, and SSIM of 0.64, compared to 26.21, 201.55 and 0.63 using the baseline method. In terms of the anatomical structure, the proposed method effectively enhances the organ shapes and boundaries and allows for a straight-forward identification of the relevant anatomical structures. We note that conventional reconstruction metrics fail to indicate the enhancement of anatomical structures. In addition to such metrics, the evaluation is expanded with assessing the organ segmentation performance. The average organ dice of the proposed method is 0.71 compared with 0.63 for the baseline model, indicating the enhancement of anatomical structures.

Uncertainty-aware deep learning for trustworthy prediction of long-term outcome after endovascular thrombectomy.

Acute ischemic stroke (AIS) is a leading global cause of mortality and morbidity. Improving long-term outcome predictions after thrombectomy can enhance treatment quality by supporting clinical decision-making. With the advent of interpretable deep learning methods in recent years, it is now possible to develop trustworthy, high-performing prediction models. This study introduces an uncertainty-aware, graph deep learning model that predicts endovascular thrombectomy outcomes using clinical features and imaging biomarkers. The model targets long-term functional outcomes, defined by the three-month modified Rankin Score (mRS), and mortality rates. A sample of 220 AIS patients in the anterior circulation who underwent endovascular thrombectomy (EVT) was included, with 81 (37%) demonstrating good outcomes (mRS ≤ 2). The performance of the different algorithms evaluated was comparable, with the maximum validation under the curve (AUC) reaching 0.87 using graph convolutional networks (GCN) for mRS prediction and 0.86 using fully connected networks (FCN) for mortality prediction. Moderate performance was obtained at admission (AUC of 0.76 using GCN), which improved to 0.84 post-thrombectomy and to 0.89 a day after stroke. Reliable uncertainty prediction of the model could be demonstrated.

Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer.

Breast cancer is the most common malignancy in women worldwide and a highly heterogeneous disease. Four different subtypes are described that differ in the expression of hormone receptors as well as the growth factor receptor HER2. Treatment modalities and survival rate depend on the subtype of breast cancer. However, it is still not clear which patients benefit from immunotherapeutic approaches such as checkpoint blockade. Thus, we aimed to decipher the immune cell signature of the different breast cancer subtypes based on high-dimensional flow cytometry followed by unbiased approaches. Here, we show that the frequency of NK cells is reduced in Luminal A and B as well as triple negative breast cancer and that the phenotype of residual NK cells is changed toward regulatory CD11b-CD16- NK cells. Further, we found higher frequencies of PD-1+ CD4+ and CD8+ T cells in triple negative breast cancer. Moreover, while Luminal A-type breast cancer was enriched for CD14+ cDC2 (named type 3 DC (DC3)), CD14- cDC2 (named DC2) were more frequent in triple negative breast cancer. In contrast, HER2-enriched breast cancer did not show major alterations in the composition of the immune cell compartment in the tumor microenvironment. These findings suggest that patients with Luminal A- and B-type as well as triple negative breast cancer might benefit from immunotherapeutic approaches targeting NK cells.

Simulation-driven training of vision transformers enables metal artifact reduction of highly truncated CBCT scans.

BACKGROUND: Due to the high attenuation of metals, severe artifacts occur in cone beam computed tomography (CBCT). The metal segmentation in CBCT projections usually serves as a prerequisite for metal artifact reduction (MAR) algorithms. PURPOSE: The occurrence of truncation caused by the limited detector size leads to the incomplete acquisition of metal masks from the threshold-based method in CBCT volume. Therefore, segmenting metal directly in CBCT projections is pursued in this work. METHODS: Since the generation of high quality clinical training data is a constant challenge, this study proposes to generate simulated digital radiographs (data I) based on real CT data combined with self-designed computer aided design (CAD) implants. In addition to the simulated projections generated from 3D volumes, 2D x-ray images combined with projections of implants serve as the complementary data set (data II) to improve the network performance. In this work, SwinConvUNet consisting of shift window (Swin) vision transformers (ViTs) with patch merging as encoder is proposed for metal segmentation. RESULTS: The model's performance is evaluated on accurately labeled test datasets obtained from cadaver scans as well as the unlabeled clinical projections. When trained on the data I only, the convolutional neural network (CNN) encoder-based networks UNet and TransUNet achieve only limited performance on the cadaver test data, with an average dice score of 0.821 and 0.850. After using both data II and data I during training, the average dice scores for the two models increase to 0.906 and 0.919, respectively. By replacing the CNN encoder with Swin transformer, the proposed SwinConvUNet reaches an average dice score of 0.933 for cadaver projections when only trained on the data I. Furthermore, SwinConvUNet has the largest average dice score of 0.953 for cadaver projections when trained on the combined data set. CONCLUSIONS: Our experiments quantitatively demonstrate the effectiveness of the combination of the projections simulated under two pathways for network training. Besides, the proposed SwinConvUNet trained on the simulated projections performs state-of-the-art, robust metal segmentation as demonstrated on experiments on cadaver and clinical data sets. With the accurate segmentations from the proposed model, MAR can be conducted even for highly truncated CBCT scans.

Network medicine-based epistasis detection in complex diseases: ready for quantum computing.

Most heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs)1-3. Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs. With NeEDL (network-based epistasis detection via local search), we leverage network medicine to inform the selection of EIs that are an order of magnitude more statistically significant compared to existing tools and consist, on average, of five SNPs. We further show that this computationally demanding task can be substantially accelerated once quantum computing hardware becomes available. We apply NeEDL to eight different diseases and discover genes (affected by EIs of SNPs) that are partly known to affect the disease, additionally, these results are reproducible across independent cohorts. EIs for these eight diseases can be interactively explored in the Epistasis Disease Atlas (https://epistasis-disease-atlas.com). In summary, NeEDL is the first application that demonstrates the potential of seamlessly integrated quantum computing techniques to accelerate biomedical research. Our network medicine approach detects higher-order EIs with unprecedented statistical and biological evidence, yielding unique insights into polygenic diseases and providing a basis for the development of improved risk scores and combination therapies.

Fetal Re-Identification in Multiple Pregnancy Ultrasound Images Using Deep Learning.

Ultrasound examinations during pregnancy can detect abnormal fetal development, which is a leading cause of perinatal mortality. In multiple pregnancies, the position of the fetuses may change between examinations. The individual fetus cannot be clearly identified. Fetal re-identification may improve diagnostic capabilities by tracing individual fetal changes. This work evaluates the feasibility of fetal re-identification on FETAL_PLANES_DB, a publicly available dataset of singleton pregnancy ultrasound images. Five dataset subsets with 6,491 images from 1,088 pregnant women and two re-identification frameworks (Torchreid, FastReID) are evaluated. FastReID achieves a mean average precision of 68.77% (68.42%) and mean precision at rank 10 score of 89.60% (95.55%) when trained on images showing the fetal brain (abdomen). Visualization with gradient-weighted class activation mapping shows that the classifiers appear to rely on anatomical features. We conclude that fetal re-identification in ultrasound images may be feasible. However, more work on additional datasets, including images from multiple pregnancies and several subsequent examinations, is required to ensure and investigate performance stability and explainability.Clinical relevance- To date, fetuses in multiple pregnancies cannot be distinguished between ultrasound examinations. This work provides the first evidence for feasibility of fetal re-identification in pregnancy ultrasound images. This may improve diagnostic capabilities in clinical practice in the future, such as longitudinal analysis of fetal changes or abnormalities.

Self-supervised MRI denoising: leveraging Stein's unbiased risk estimator and spatially resolved noise maps.

Thermal noise caused by the imaged object is an intrinsic limitation in magnetic resonance imaging (MRI), resulting in an impaired clinical value of the acquisitions. Recently, deep learning (DL)-based denoising methods achieved promising results by extracting complex feature representations from large data sets. Most approaches are trained in a supervised manner by directly mapping noisy to noise-free ground-truth data and, therefore, require extensive paired data sets, which can be expensive or infeasible to obtain for medical imaging applications. In this work, a DL-based denoising approach is investigated which operates on complex-valued reconstructed magnetic resonance (MR) images without noise-free target data. An extension of Stein's unbiased risk estimator (SURE) and spatially resolved noise maps quantifying the noise level with pixel accuracy were employed during the training process. Competitive denoising performance was achieved compared to supervised training with mean squared error (MSE) despite optimizing the model without noise-free target images. The proposed DL-based method can be applied for MR image enhancement without requiring noise-free target data for training. Integrating the noise maps as an additional input channel further enables the regulation of the desired level of denoising to adjust to the preference of the radiologist.

Evolutionary optimization and long-term stabilization of a white-light seeded two-stage OPCPA seed laser.

Ultrafast laser systems, such as optical parametric chirped pulse amplifiers (OPCPA), are complex tools. Optimizing laser performance for a given application is often plagued by intricate couplings between different output parameters, making simultaneous control of multiple pulse properties difficult. Here, we experimentally demonstrate an autonomous tuning procedure of a white-light seeded two-stage OPCPA using an evolutionary strategy to reliably reach an optimized working point. We use the data collected during the tuning procedure to calibrate a performance model of the laser system, which we then apply to stabilize the intricately coupled laser output energy and spectrum simultaneously. Our approach ensures reliable day-to-day operation at optimized working points without manual tuning. We demonstrate shot-to-shot energy stability of <0.18 % rms, in combination with <25 pm rms wavelength stability and <0.2 % rms bandwidth stability during multi-day operation.

Out-of-plane multilayer-dielectric-grating compressor for ultrafast Ti:sapphire pulses.

Extreme heat loads on optics, in particular the final pulse compression gratings, are a major hurdle to overcome in the ongoing push towards high average power (kW) and high repetition rate (kHz) operation of terawatt-class Ti:sapphire lasers. Multilayer dielectric (MLD) diffraction gratings have been suggested as a potential alternative to traditionally gold-coated compressor gratings, which are plagued by high energy absorption in the top gold layer. However, to support the required bandwidth (and ultimately the desired pulse duration) with MLD gratings, the gratings have to be operated in an out-of-plane geometry near the Littrow angle. Here, we report on the design of an MLD-based out-of-plane test compressor and a matching custom stretcher. We present a full characterization of the MLD compressor, focusing on its spectral transmission and the significance of laser pulse polarization in the out-of-plane geometry. To demonstrate compression of 40 µJ pulses centered at 800 nm wavelength to 26 fs pulse duration, we use the compressor with an MLD and gold grating configuration, and fully characterize the compressed pulses. Extrapolating our results indicates that MLD-grating-based out-of-plane compressors can support near-transform-limited pulses with sub-30 fs duration and good quality, demonstrating the viability of this concept for kW-level ultrafast Ti:sapphire laser systems.