Among the symptoms that can occur in Parkinson's disease (PD), Freezing of Gait (FOG) is a disabling phenomenon affecting a large proportion of patients, and it remains not fully understood. Accurate classification of FOG in PD is crucial for tailoring effective interventions and is necessary for a better understanding of its underlying mechanisms. In the present work, we applied four Machine Learning (ML) classifiers (Decision Tree - DT, Random Forest - RF, Multilayer Perceptron - MLP, Logistic Regression - LOG) to different four metrics derived from resting-state functional Magnetic Resonance Imaging (rs-fMRI) data processing to assess their accuracy in automatically classifying PD patients based on the presence or absence of Freezing of Gait (FOG). To validate our approach, we applied the same methodologies to distinguish PD patients from a group of Healthy Subject (HS). The performance of the four ML algorithms was validated by repeated k-fold cross-validation on randomly selected independent training and validation subsets. The results showed that when discriminating PD from HS, the best performance was achieved using RF applied to fractional Amplitude of Low-Frequency Fluctuations (fALFF) data (AUC 96.8 ± 2 %). Similarly, when discriminating PD-FOG from PD-nFOG, the RF algorithm was again the best performer on all four metrics, with AUCs above 90 %. Finally, trying to unbox how AI system black-box choices were made, we extracted features' importance scores for the best-performing method(s) and discussed them based on the results obtained to date in rs-fMRI studies on FOG in PD and, more generally, in PD. In summary, regions that were more frequently selected when differentiating both PD from HS and PD-FOG from PD-nFOG patients were mainly relevant to the extrapyramidal system, as well as visual and default mode networks. In addition, the salience network and the supplementary motor area played an additional major role in differentiating PD-FOG from PD-nFOG patients.

Due to population aging, the increasing prevalence of Alzheimer's Disease (AD) and related dementias are major public health concerns. Dietary consumption of antioxidant nutrients, in particular the carotenoid β-carotene, has been associated with lower age-related neurocognitive decline. What is unclear, however, is the extent to which antioxidant nutrients may exert neuroprotective effects via their influence on established indicators of age-related changes in brain tissue. This study thus tested associations of circulating β-carotene and other nutrients with a structural neuroimaging indicator of brain age derived from cross-validated machine learning models trained to predict chronological age from brain tissue morphology in independent cohorts. Midlife adults (N=132, aged 30.4 to 50.8 years, 59 female at birth) underwent a structural magnetic resonance imaging (MRI) protocol and fasting phlebotomy to assess plasma concentrations of β-carotene, retinol, γ-tocopherol, ⍺-tocopherol, and β-cryptoxanthin. In regression analyses adjusting for chronological age, sex at birth, smoking status, MRI image quality, season of testing, annual income, and education, greater circulating levels of β-carotene were associated with a lower (i.e., younger) predicted brain age (β=-0.23, 95% CI=-0.40 to -0.07, P=0.006). Other nutrients were not statistically associated with brain age, and results persisted after additional covariate control for body mass index, cortical volume, and cortical thickness. These cross-sectional findings are consistent with the possibility that dietary intake of β-carotene may be associated with slower biological aging at the level of the brain, as reflected by a neuroimaging indicator of brain age.

Purpose: Deep learning has demonstrated strong potential for MRI reconstruction, but conventional supervised learning methods require high-quality reference images, which are often unavailable in practice. Self-supervised learning offers an alternative, yet its performance degrades at high acceleration rates. To overcome these limitations, we propose hybrid learning, a novel two-stage training framework that combines self-supervised and supervised learning for robust image reconstruction. Methods: Hybrid learning is implemented in two sequential stages. In the first stage, self-supervised learning is employed to generate improved images from noisy or undersampled reference data. These enhanced images then serve as pseudo-ground truths for the second stage, which uses supervised learning to refine reconstruction performance and support higher acceleration rates. We evaluated hybrid learning in two representative applications: (1) accelerated 0.55T spiral-UTE lung MRI using noisy reference data, and (2) 3D T1 mapping of the brain without access to fully sampled ground truth. Results: For spiral-UTE lung MRI, hybrid learning consistently improved image quality over both self-supervised and conventional supervised methods across different acceleration rates, as measured by SSIM and NMSE. For 3D T1 mapping, hybrid learning achieved superior T1 quantification accuracy across a wide dynamic range, outperforming self-supervised learning in all tested conditions. Conclusions: Hybrid learning provides a practical and effective solution for training deep MRI reconstruction networks when only low-quality or incomplete reference data are available. It enables improved image quality and accurate quantitative mapping across different applications and field strengths, representing a promising technique toward broader clinical deployment of deep learning-based MRI.

The low proton density and high signal decay rate of pulmonary tissue have previously hampered the application of magnetic resonance imaging (MRI) in the clinical evaluation of lung disorders. With the continuing technical advances in scanners, coils, pulse sequences, and image postprocessing, pulmonary MRI can provide structural and functional information with faster imaging speed and improved image quality, which has shown potential to be an alternative and complementary diagnostic method to chest computed tomography (CT). Compared with CT, MRI does not involve ionizing radiation, making it particularly suitable for pediatric patients, pregnant women, and individuals requiring longitudinal monitoring. This narrative review focuses on recent advances in techniques and clinical applications for pulmonary MRI in lung diseases, including lung parenchymal and pulmonary vascular diseases. Future developments, including artificial intelligence-driven technological optimization and assisted diagnosis, hardware advancements, and clinical biomarkers validation, hold the potential to further enhance the clinical utility of pulmonary MRI. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

Online adaptive magnetic resonance-guided radiotherapy (MRgRT) has emerged as a state-of-the-art treatment option for multiple tumour entities, accounting for daily anatomical and tumour volume changes, thus allowing sparing of relevant organs at risk (OARs). However, the annotation of treatment-relevant anatomical structures in context of online plan adaptation remains challenging, often relying on commercial segmentation solutions due to limited availability of clinically validated alternatives. The aim of this study was to investigate whether an open-source artificial intelligence (AI) segmentation network can compete with the annotation accuracy of a commercial solution, both trained on the identical dataset, questioning the need for commercial models in clinical practice. For 47 pelvic patients, T2w MR imaging data acquired on a 1.5 T MR-Linac were manually contoured, identifying prostate, seminal vesicles, rectum, anal canal, bladder, penile bulb, and bony structures. These training data were used for the generation of an in-house AI segmentation model, a nnU-Net with residual encoder architecture featuring a streamlined single image inference pipeline, and re-training of a commercial solution. For quantitative evaluation, 20 MR images were contoured by a radiation oncologist, considered as ground truth contours (GTC) and compared with the in-house/commercial AI-based contours (iAIC/cAIC) using Dice Similarity Coefficient (DSC), 95% Hausdorff distances (HD95), and surface DSC (sDSC). For qualitative evaluation, four radiation oncologists assessed the usability of OAR/target iAIC within an online adaptive workflow using a four-point Likert scale: (1) acceptable without modification, (2) requiring minor adjustments, (3) requiring major adjustments, and (4) not usable. Patient-individual annotations were generated in a median [range] time of 23 [16-34] s for iAIC and 152 [121-198] s for cAIC, respectively. OARs showed a maximum median DSC of 0.97/0.97 (iAIC/cAIC) for bladder and minimum median DSC of 0.78/0.79 (iAIC/cAIC) for anal canal/penile bulb. Maximal respectively minimal median HD95 were detected for rectum with 17.3/20.6 mm (iAIC/cAIC) and for bladder with 5.6/6.0 mm (iAIC/cAIC). Overall, the average median DSC/HD95 values were 0.87/11.8mm (iAIC) and 0.83/10.2mm (cAIC) for OAR/targets and 0.90/11.9mm (iAIC) and 0.91/16.5mm (cAIC) for bony structures. For a tolerance of 3 mm, the highest and lowest sDSC were determined for bladder (iAIC:1.00, cAIC:0.99) and prostate in iAIC (0.89) and anal canal in cAIC (0.80), respectively. Qualitatively, 84.8% of analysed contours were considered as clinically acceptable for iAIC, while 12.9% required minor and 2.3% major adjustments or were classed as unusable. Contour-specific analysis showed that iAIC achieved the highest mean scores with 1.00 for the anal canal and the lowest with 1.61 for the prostate. This study demonstrates that open-source segmentation framework can achieve comparable annotation accuracy to commercial solutions for pelvic anatomy in online adaptive MRgRT. The adapted framework not only maintained high segmentation performance, with 84.8% of contours accepted by physicians or requiring only minor corrections (12.9%) but also enhanced clinical workflow efficiency of online adaptive MRgRT through reduced inference times. These findings establish open-source frameworks as viable alternatives to commercial systems in supervised clinical workflows.

To evaluate spectrum bias in stroke MRI analysis by excluding cases with uncertain acute ischemic lesions (AIL) and examining patient, imaging, and lesion factors associated with these cases. This single-center retrospective observational study included adults with brain MRIs for suspected stroke between January 2020 and April 2022. Diagnostic uncertain AIL were identified through reader disagreement or low certainty grading by a radiology resident, a neuroradiologist, and the original radiology report consisting of various neuroradiologists. A commercially available deep learning tool analyzing brain MRIs for AIL was evaluated to assess the impact of excluding uncertain cases on diagnostic odds ratios. Patient-related, MRI acquisition-related, and lesion-related factors were analyzed using the Wilcoxon rank sum test, χ2 test, and multiple logistic regression. The study was approved by the National Committee on Health Research Ethics. In 989 patients (median age 73 (IQR: 59-80), 53% female), certain AIL were found in 374 (38%), uncertain AIL in 63 (6%), and no AIL in 552 (56%). Excluding uncertain cases led to a four-fold increase in the diagnostic odds ratio (from 68 to 278), while a simulated case-control design resulted in a six-fold increase compared to the full disease spectrum (from 68 to 431). Independent factors associated with uncertain AIL were MRI artifacts, smaller lesion size, older lesion age, and infratentorial location. Excluding uncertain cases leads to a four-fold overestimation of the diagnostic odds ratio. MRI artifacts, smaller lesion size, infratentorial location, and older lesion age are associated with uncertain AIL and should be accounted for in validation studies.

Diffusion models (DMs) excel in pixel-level and spatial tasks and are proven feature extractors for 2D image discriminative tasks when pretrained. However, their capabilities in 3D MRI discriminative tasks remain largely untapped. This study seeks to assess the effectiveness of DMs in this underexplored area. We use 59830 T1-weighted MR images (T1WIs) from the extensive, yet unlabeled, UK Biobank dataset. Additionally, we apply 369 T1WIs from the BraTS2020 dataset specifically for brain tumor classification, and 421 T1WIs from the ADNI1 dataset for the diagnosis of Alzheimer's disease. Firstly, a high-performing denoising diffusion probabilistic model (DDPM) with a U-Net backbone is pretrained on the UK Biobank, then fine-tuned on the BraTS2020 and ADNI1 datasets. Afterward, we assess its feature representation capabilities for discriminative tasks using linear probes. Finally, we accordingly introduce a novel fusion module, named CATS, that enhances the U-Net representations, thereby improving performance on discriminative tasks. Our DDPM produces synthetic images of high quality that match the distribution of the raw datasets. Subsequent analysis reveals that DDPM features extracted from middle blocks and smaller timesteps are of high quality. Leveraging these features, the CATS module, with just 1.7M additional parameters, achieved average classification scores of 0.7704 and 0.9217 on the BraTS2020 and ADNI1 datasets, demonstrating competitive performance with that of the representations extracted from the transferred DDPM model, as well as the 33.23M parameters ResNet18 trained from scratch. We have found that pretraining a DM on a large-scale dataset and then fine-tuning it on limited data from discriminative datasets is a viable approach for MRI data. With these well-performing DMs, we show that they excel not just in generation tasks but also as feature extractors when combined with our proposed CATS module.

High-grade gliomas, particularly glioblastoma (MeSH:Glioblastoma), are among the most aggressive and lethal central nervous system tumors, necessitating advanced diagnostic and prognostic strategies. This systematic review and epistemic meta-analysis explore the integration of Artificial Intelligence (AI) and Radiomics Inter-field (AIRI) to enhance predictive modeling for tumor progression. A comprehensive literature search identified 19 high-quality studies, which were analyzed to evaluate radiomic features and machine learning models in predicting overall survival (OS) and progression-free survival (PFS). Key findings highlight the predictive strength of specific MRI-derived radiomic features such as log-filter and Gabor textures and the superior performance of Support Vector Machines (SVM) and Random Forest (RF) models, achieving high accuracy and AUC scores (e.g., 98% AUC and 98.7% accuracy for OS). This research demonstrates the current state of the AIRI field and shows that current articles report their results with different performance indicators and metrics, making outcomes heterogenous and hard to integrate knowledge. Additionally, it was explored that today some articles use biased methodologies. This study proposes a structured AIRI development roadmap and guidelines, to avoid bias and make results comparable, emphasizing standardized feature extraction and AI model training to improve reproducibility across clinical settings. By advancing precision medicine, AIRI integration has the potential to refine clinical decision-making and enhance patient outcomes.

Uncertainty assessment of deep learning autosegmentation (DLAS) models can support contour corrections in adaptive radiotherapy (ART), e.g. by utilizing Monte Carlo Dropout (MCD) uncertainty maps. However, poorly calibrated uncertainties at the patient level often render these clinically nonviable. We evaluated population-based and patient-specific DLAS accuracy and uncertainty calibration and propose a patient-specific post-training uncertainty calibration method for DLAS in ART.&#xD;&#xD;Approach. The study included 122 lung cancer patients treated with a low-field MR-linac (80/19/23 training/validation/test cases). Ten single-label 3D-U-Net population-based baseline models (BM) were trained with dropout using planning MRIs (pMRIs) and contours for nine organs-at-riks (OARs) and gross tumor volumes (GTVs). Patient-specific models (PS) were created by fine-tuning BMs with each test patient's pMRI. Model uncertainty was assessed with MCD, averaged into probability maps. Uncertainty calibration was evaluated with reliability diagrams and expected calibration error (ECE). A proposed post-training calibration method rescaled MCD probabilities for fraction images in BM (calBM) and PS (calPS) after fitting reliability diagrams from pMRIs. All models were evaluated on fraction images using Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95) and ECE. Metrics were compared among models for all OARs combined (n=163), and the GTV (n=23), using Friedman and posthoc-Nemenyi tests (α=0.05).&#xD;&#xD;Main results. For the OARs, patient-specific fine-tuning significantly (p<0.001) increased median DSC from 0.78 (BM) to 0.86 (PS) and reduced HD95 from 14mm (BM) to 6.0mm (PS). Uncertainty calibration achieved substantial reductions in ECE, from 0.25 (BM) to 0.091 (calBM) and 0.22 (PS) to 0.11 (calPS) (p<0.001), without significantly affecting DSC or HD95 (p>0.05). For the GTV, BM performance was poor (DSC=0.05) but significantly (p<0.001) improved with PS training (DSC=0.75) while uncertainty calibration reduced ECE from 0.22 (PS) to 0.15 (calPS) (p=0.45).&#xD;&#xD;Significance. Post-training uncertainty calibration yields geometrically accurate DLAS models with well-calibrated uncertainty estimates, crucial for ART applications.

Previous resting state functional MRI (rs-fMRI) analyses of the basal ganglia in Parkinson's disease heavily relied on T1-weighted imaging (T1WI) atlases. However, subcortical structures are characterized by subtle contrast differences, making their accurate delineation challenging on T1WI. In this study, we aimed to introduce and validate a method that incorporates quantitative susceptibility mapping (QSM) into the rs-fMRI analytical pipeline to achieve precise subcortical nuclei segmentation and improve the stability of RSFC measurements in Parkinson's disease. A total of 321 participants (148 patients with Parkinson's Disease and 173 normal controls) were enrolled. We performed cross-modal registration at the individual level for rs-fMRI to QSM (FUNC2QSM) and T1WI (FUNC2T1), respectively.The consistency and accuracy of resting state functional connectivity (RSFC) measurements in two registration approaches were assessed by intraclass correlation coefficient and mutual information. Bootstrap analysis was performed to validate the stability of the RSFC differences between Parkinson's disease and normal controls. RSFC-based machine learning models were constructed for Parkinson's disease classification, using optimized hyperparameters (RandomizedSearchCV with 5-fold cross-validation). The consistency of RSFC measurements between the two registration methods was poor, whereas the QSM-guided approach showed better mutual information values, suggesting higher registration accuracy. The disruptions of RSFC identified with the QSM-guided approach were more stable and reliable, as confirmed by bootstrap analysis. In classification models, the QSM-guided method consistently outperformed the T1WI-guided method, achieving higher test-set ROC-AUC values (FUNC2QSM: 0.87-0.90, FUNC2T1: 0.67-0.70). The QSM-guided approach effectively enhanced the accuracy of subcortical segmentation and the stability of RSFC measurement, thus facilitating future biomarker development in Parkinson's disease.