Postmortem neuropathological examination, while the gold standard for diagnosing neurodegenerative diseases, often relies on limited regional sampling that may miss critical areas affected by Alzheimer's disease and related disorders. Ultra-high resolution postmortem MRI can help identify regions that fall outside the diagnostic sampling criteria for additional histopathologic evaluation. However, there are no standardized guidelines for integrating histology and MRI in a traditional brain bank. We developed a comprehensive protocol for whole hemisphere postmortem 7T MRI-guided histopathological sampling with whole-slide digital imaging and histopathological analysis, providing a reliable pipeline for high-volume brain banking in heterogeneous brain tissue. Our method uses patient-specific 3D printed molds built from postmortem MRI, allowing standardized tissue processing with a permanent spatial reference frame. To facilitate pathology-MRI association studies, we created a semi-automated MRI to histology registration pipeline and developed a quantitative pathology scoring system using weakly supervised deep learning. We validated this protocol on a cohort of 29 brains with diagnosis on the AD spectrum that revealed correlations between cortical thickness and phosphorylated tau accumulation. This pipeline has broad applicability across neuropathological research and brain banking, facilitating large-scale studies that integrate histology with neuroimaging. The innovations presented here provide a scalable and reproducible approach to studying postmortem brain pathology, with implications for advancing diagnostic and therapeutic strategies for Alzheimer's disease and related disorders.

Permanent prostate brachytherapy has inherent intraoperative organ deformation due to the inflatable trans-rectal ultrasound probe cover. Since the majority of the dose is delivered postoperatively with no deformation, the dosimetry approved at the time of implant may not accurately represent the dose delivered to the target and organs at risk. We aimed to evaluate the biological effect of the prostate deformation and its correlation with patient-reported outcomes. We prospectively acquired ultrasound images of the prostate pre- and postprobe cover inflation for 27 patients undergoing I-125 seed implant. The coordinates of implanted seeds from approved clinical plan were transferred to deformation-corrected prostate to simulate the actual dosimetry using a machine learning-based deformable image registration. The DVHs of both sets of plans were reduced to biologically effective dose (BED) distribution and subsequently to Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) metrics. The change in fourteen patient-reported rectal and urinary symptoms between pretreatment to 6 months post-op time points were correlated with the TCP and NTCP metrics using the area under the curve (AUC) and odds ratio (OR). Between the clinical and the deformation corrected research plans, the mean TCP decreased by 9.4% (p < 0.01), whereas mean NTCP of rectum decreased by 10.3% and that of urethra increased by 16.3%, respectively (p < 0.01). For the diarrhea symptom, the deformation corrected research plans showed AUC=0.75 and OR = 8.9 (1.3-58.8) for the threshold NTCP>20%, while the clinical plan showed AUC=0.56 and OR = 1.4 (0.2 to 9.0). For the symptom of urinary control, the deformation corrected research plans showed AUC = 0.70, OR = 6.9 (0.6 to 78.0) for the threshold of NTCP>15%, while the clinical plan showed AUC = 0.51 and no positive OR. Taking organ deformation into consideration, clinical brachytherapy plans showed worse tumor coverage, worse urethra sparing but better rectal sparing. The deformation corrected research plans showed a stronger correlation with the patient-reported outcome than the clinical plans for the symptoms of diarrhea and urinary control.

Deformable image registration (DIR) is an enabling technology in many diagnostic and therapeutic tasks. Despite this, DIR algorithms have limited clinical use, largely due to a lack of benchmark datasets for quality assurance during development. DIRs of intra-patient abdominal CTs are among the most challenging registration scenarios due to significant organ deformations and inconsistent image content. To support future algorithm development, here we introduce our first-of-its-kind abdominal CT DIR benchmark dataset, comprising large numbers of highly accurate landmark pairs on matching blood vessel bifurcations. Abdominal CT image pairs of 30 patients were acquired from several publicly available repositories as well as the authors' institution with IRB approval. The two CTs of each pair were originally acquired for the same patient but on different days. An image processing workflow was developed and applied to each CT image pair: (1) Abdominal organs were segmented with a deep learning model, and image intensity within organ masks was overwritten. (2) Matching image patches were manually identified between two CTs of each image pair. (3) Vessel bifurcation landmarks were labeled on one image of each image patch pair. (4) Image patches were deformably registered, and landmarks were projected onto the second image. (5) Landmark pair locations were refined manually or with an automated process. This workflow resulted in 1895 total landmark pairs, or 63 per case on average. Estimates of the landmark pair accuracy using digital phantoms were 0.7 mm ± 1.2 mm. The data are published in Zenodo at https://doi.org/10.5281/zenodo.14362785. Instructions for use can be found at https://github.com/deshanyang/Abdominal-DIR-QA. This dataset is a first-of-its-kind for abdominal DIR validation. The number, accuracy, and distribution of landmark pairs will allow for robust validation of DIR algorithms with precision beyond what is currently available.

Limited DXA access hinders osteoporosis screening. This proof-of-concept study proposes using widely available knee X-rays for opportunistic Bone Mineral Density (BMD) estimation via deep learning, emphasizing robust uncertainty quantification essential for clinical use. An EfficientNet model was trained on the OAI dataset to predict BMD from bilateral knee radiographs. Two Test-Time Augmentation (TTA) methods were compared: traditional averaging and a multi-sample approach. Crucially, Split Conformal Prediction was implemented to provide statistically rigorous, patient-specific prediction intervals with guaranteed coverage. Results showed a Pearson correlation of 0.68 (traditional TTA). While traditional TTA yielded better point predictions, the multi-sample approach produced slightly tighter confidence intervals (90%, 95%, 99%) while maintaining coverage. The framework appropriately expressed higher uncertainty for challenging cases. Although anatomical mismatch between knee X-rays and standard DXA limits immediate clinical use, this method establishes a foundation for trustworthy AI-assisted BMD screening using routine radiographs, potentially improving early osteoporosis detection.

The assessment of resting energy expenditure (REE) is a challenging task with the current existing methods. The reference method, indirect calorimetry (IC), is not widely available, and other surrogates, such as equations and bioimpedance (BIA) show poor agreement with IC. Body composition (BC), in particular muscle mass, plays an important role in REE. In recent years, computed tomography (CT) has emerged as a reliable tool for BC assessment, but its usefulness for the REE evaluation has not been examined. In the present study we have explored the usefulness of CT-scan imaging to assess the REE using AI machine-learning models. Single-centre observational cross-sectional pilot study from January to June 2022, including 90 fasting, clinically stable adults (≥18 years) with no contraindications for indirect calorimetry (IC), bioimpedance (BIA), or abdominal CT-scan. REE was measured using classical predictive equations, IC, BIA and skeletal CT-scan. The proposed model was based on a second-order linear regression with different input parameters, and the output corresponds to the estimated REE. The model was trained and tested using a cross-validation one-vs-all strategy including subjects with different characteristics. Data from 90 subjects were included in the final analysis. Bland-Altman plots showed that the CT-based estimation model had a mean bias of 0 kcal/day (LoA: -508.4 to 508.4) compared with IC, indicating better agreement than most predictive equations and similar agreement to BIA (bias 53.4 kcal/day, LoA: -475.7 to 582.4). Surprisingly, gender and BMI, ones of the mains variables included in all the BIA algorithms and mathematical equations were not relevant variables for REE calculated by means of AI coupled to skeletal CT scan. These findings were consistent with the results of other performance metrics, including mean absolute error (MAE), root mean square error (RMSE), and Lin's concordance correlation coefficient (CCC), which also favored the CT-based method over conventional equations. Our results suggest that the analysis of a CT-scan image by means of machine learning model is a reliable tool for the REE estimation. These findings have the potential to significantly change the paradigm and guidelines for nutritional assessment.

Determining the 3D pose of a patient from a limited set of 2D X-ray images is a critical task in interventional settings. While preoperative volumetric imaging (e.g., CT and MRI) provides precise 3D localization and visualization of anatomical targets, these modalities cannot be acquired during procedures, where fast 2D imaging (X-ray) is used instead. To integrate volumetric guidance into intraoperative procedures, we present PolyPose, a simple and robust method for deformable 2D/3D registration. PolyPose parameterizes complex 3D deformation fields as a composition of rigid transforms, leveraging the biological constraint that individual bones do not bend in typical motion. Unlike existing methods that either assume no inter-joint movement or fail outright in this under-determined setting, our polyrigid formulation enforces anatomically plausible priors that respect the piecewise rigid nature of human movement. This approach eliminates the need for expensive deformation regularizers that require patient- and procedure-specific hyperparameter optimization. Across extensive experiments on diverse datasets from orthopedic surgery and radiotherapy, we show that this strong inductive bias enables PolyPose to successfully align the patient's preoperative volume to as few as two X-ray images, thereby providing crucial 3D guidance in challenging sparse-view and limited-angle settings where current registration methods fail.

'Brain age' is a biological clock typically used to describe brain health with one number, but its relationship with established gradients of cortical organization remains unclear. We address this gap by leveraging a data-driven, region-specific brain age approach in 335 neurologically intact adults, using a convolutional neural network (volBrain) to estimate regional brain ages directly from structural MRI without a predefined set of morphometric properties. Six distinct gradients of brain aging are replicated in two independent cohorts. Spatial patterns of accelerated brain aging in older adults quantitatively align with the archetypal sensorimotor-to-association axis of cortical organization. Other brain aging gradients reflect neurobiological hierarchies such as gene expression and externopyramidization. Participant-level correspondences to brain age gradients are associated with cognitive and sensorimotor performance and explained behavioral variance more effectively than global brain age. These results suggest that regional brain age patterns reflect fundamental principles of cortical organization and behavior.

Determining the 3D pose of a patient from a limited set of 2D X-ray images is a critical task in interventional settings. While preoperative volumetric imaging (e.g., CT and MRI) provides precise 3D localization and visualization of anatomical targets, these modalities cannot be acquired during procedures, where fast 2D imaging (X-ray) is used instead. To integrate volumetric guidance into intraoperative procedures, we present PolyPose, a simple and robust method for deformable 2D/3D registration. PolyPose parameterizes complex 3D deformation fields as a composition of rigid transforms, leveraging the biological constraint that individual bones do not bend in typical motion. Unlike existing methods that either assume no inter-joint movement or fail outright in this under-determined setting, our polyrigid formulation enforces anatomically plausible priors that respect the piecewise rigid nature of human movement. This approach eliminates the need for expensive deformation regularizers that require patient- and procedure-specific hyperparameter optimization. Across extensive experiments on diverse datasets from orthopedic surgery and radiotherapy, we show that this strong inductive bias enables PolyPose to successfully align the patient's preoperative volume to as few as two X-ray images, thereby providing crucial 3D guidance in challenging sparse-view and limited-angle settings where current registration methods fail.

Magnetic resonance (MR) tagging is an imaging technique for noninvasively tracking tissue motion in vivo by creating a visible pattern of magnetization saturation (tags) that deforms with the tissue. Due to longitudinal relaxation and progression to steady-state, the tags and tissue brightnesses change over time, which makes tracking with optical flow methods error-prone. Although Fourier methods can alleviate these problems, they are also sensitive to brightness changes as well as spectral spreading due to motion. To address these problems, we introduce the brightness-invariant tracking estimation (BRITE) technique for tagged MRI. BRITE disentangles the anatomy from the tag pattern in the observed tagged image sequence and simultaneously estimates the Lagrangian motion. The inherent ill-posedness of this problem is addressed by leveraging the expressive power of denoising diffusion probabilistic models to represent the probabilistic distribution of the underlying anatomy and the flexibility of physics-informed neural networks to estimate biologically-plausible motion. A set of tagged MR images of a gel phantom was acquired with various tag periods and imaging flip angles to demonstrate the impact of brightness variations and to validate our method. The results show that BRITE achieves more accurate motion and strain estimates as compared to other state of the art methods, while also being resistant to tag fading.

This paper presents a novel method for monocular patient-to-image intraoperative registration, specifically designed to operate without any external hardware tracking equipment or fiducial point markers. Leveraging a synthetic microscopy surgical scene dataset with a wide range of transformations, our approach directly maps preoperative CT scans to 2D intraoperative surgical frames through a lightweight neural network for real-time cochlear implant surgery guidance via a zero-shot learning approach. Unlike traditional methods, our framework seamlessly integrates with monocular surgical microscopes, making it highly practical for clinical use without additional hardware dependencies and requirements. Our method estimates camera poses, which include a rotation matrix and a translation vector, by learning from the synthetic dataset, enabling accurate and efficient intraoperative registration. The proposed framework was evaluated on nine clinical cases using a patient-specific and cross-patient validation strategy. Our results suggest that our approach achieves clinically relevant accuracy in predicting 6D camera poses for registering 3D preoperative CT scans to 2D surgical scenes with an angular error within 10 degrees in most cases, while also addressing limitations of traditional methods, such as reliance on external tracking systems or fiducial markers.