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NMR in Biomedicine

Wiley

Preprints posted in the last 30 days, ranked by how well they match NMR in Biomedicine's content profile, based on 24 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Increased diffusion in livers with advanced fibrosis: pre-clinical and clinical observations with diffusion MRI

Xu, F.-Y.; Wang, Y.-X.

2026-04-01 biophysics 10.64898/2026.03.30.715426 medRxiv
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Despite the increased water content in fibrotic livers, numerous studies reported a decrease in ADC (apparent diffusion coefficient) in liver fibrosis. We argue that the ADC decrease in fibrotic livers is due to the T2 shine-through of ADC, as the longer T2 in liver fibrosis leads to less signal decay between the low and high b-value images. The metric slow diffusion coefficient (SDC) was proposed to mitigate the difficulties associated with this T2 shine-through of ADC. This study calculated ADC and SDC of one rat study with liver fibrosis induced by biliary duct ligation (BDL), and three sets of human liver fibrosis data. To tease out the menopausal effect on SDC, only the results of mens livers were analysed for the human datasets. The rat study showed, liver ADC decreased stepwise (in weeks after BDL procedure) following fibrosis induction, SDC increased stepwise. In human studies, all three datasets consistently showed advanced fibrosis had an ADC lower than that of earlier stage fibrosis; advanced fibrosis had a SDC higher than that of earlier stage fibrosis. When each liver SDC datum was normalized by the mean value of the controls without fibrosis, and the three human datasets were summed together, stage-1 liver fibrosis had a normalized SDC value lower than that of the controls, and there was a stepwise increase of SDC value from stage-1 liver fibrosis to stage-4 liver fibrosis. It is known that liver fibrosis is associated with lower perfusion, higher iron/susceptibility, and higher water content, and these three factors all contribute to the lower ADC measure. Higher iron/susceptibility lowers SDC measure, whereas higher water content elevates SDC measure. It is likely that for early-stage fibrosis, the net effect of susceptibility and water leads to a lower SDC, while for advanced fibrosis, the net effect leads to a higher SDC.

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Comparison of HDO production from Glucose as a marker of Glucose metabolism

SHARMA, G.; Malut, V.; Madheswaran, M.; Peters, H.; Naik, S.; Nulk, A. R.; Kodibagkar, V. D.; Bankson, J. A.; Merritt, M. E.

2026-04-07 neuroscience 10.64898/2026.04.03.716329 medRxiv
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PURPOSEGlycolytic production of HDO from the metabolism of perdeuterated glucose provides a means for metabolic imaging with 2H MRI. The present study compared HDO production from a cost-efficient [2,3,4,6,6-2H5]glucose with [2H7]glucose in vitro and in vivo. METHODS2H NMR spectroscopy was performed to measure glucose consumption, lactate, and HDO production in the SFxL glioblastoma cell line. In vivo studies in healthy mice using 2H magnetic resonance spectroscopy were performed at 11.1 T after administering a bolus of either metabolic contrast agent. In vivo metabolite levels were quantified using unlocalized and slice-selective localized spectra. RESULTSOur in vitro results demonstrated similar glucose consumption and HDO production kinetics, although significant differences in lactate labeling were observed. The in vivo study showed comparable glucose consumption and HDO production kinetics following tail-vein bolus administration of either metabolic contrast agent, while lactate was not detected in the brain. CONCLUSION[2,3,4,6,6-2H5]glucose shows comparable HDO production to [2H7]glucose, while offering lower cost and reduced spectral complexity. These findings place [2,3,4,6,6-2H5]glucose as an alternative to [2H7]glucose for HDO-based DMI studies.

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Noninvasive thigh temperature mapping after cold water immersion and subsequent exercise using magnetic resonance spectrometry.

Giraud, D.; Hays, A.; Nussbaumer, M.; Kopp, E.; Corbin, N.; Le Fur, Y.; Gardarein, J.-L.; Ozenne, V.

2026-04-02 physiology 10.64898/2026.03.31.714134 medRxiv
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Heat-related illnesses pose a significant public health challenge in Europe, resulting in increased mortality. Although cold water immersion (CWI) is the most effective treatment for heat stroke, its clinical use is limited. A better understanding of temperature changes in the peripheral body regions can lead to more effective CWI application. Nevertheless, most muscle temperature measurement techniques are invasive. This study evaluated magnetic resonance spectroscopy (MRS) for non-invasive assessment of intramuscular temperature during cold stress and rewarming. Nine healthy volunteers (7 men, 2 women) participated in three 3T MRI sessions: baseline (PRE), immediately after 15 minutes of CWI at 10 degrees to the iliac crest (POST-CWI), and following 100-Watt cycling (POST-cycling). Each scan session included T1w and localized spectroscopy acquisitions in the right thigh. Absolute temperature was estimated from the proton resonance frequency shift between water and creatine peaks. The measurements were split into three groups of voxels, defined as follows: close to the top (TL), bottom (BL), or central (DL) thigh positions. Measurement depth showed a location main effect (p<0.001, p^2=0.40), with DL (35.4[5.9] mm) significantly deeper than TL (22.5[4.2] mm) and BL (25.3[5.1] mm), remaining constant across phases. Temperature decreased significantly from PRE to POST-CWI across all locations (TL: p<0.001, d=2.74; BL: p<0.001, d=1.84; DL: p<0.005, d=1.14). Post-cycling temperature increased at all sites compared to POST-CWI (DL: p=0.040, d=1.06; TL: p<0.001, d=1.7; BL: p<0.001, d=1.80), though TL remained lower than PRE (p<0.017, d=1.48). During POST-CWI, DL showed a significantly higher temperature than TL (p<0.001, d=2.13) and BL (p<0.001, d=2.06). These findings demonstrate that MRS-based temperature mapping provides unique anatomical and thermal characterization of muscle during thermoregulatory stress. While results are promising for understanding CWI mechanisms, validation in larger cohorts is necessary to establish clinical reliability and reproducibility for heat illness management.

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Quantitative T2 Brain Mapping with Simultaneous RF Estimation Using Dual Interleaved Steady States at 7T MRI

Yacobi, D.; Schmidt, R.

2026-03-30 radiology and imaging 10.64898/2026.03.27.26349590 medRxiv
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Objective. Quantitative T2 mapping plays a critical role in brain imaging for assessing a range of neurological conditions, including neurodegenerative diseases, demyelinating disorders, and cerebrovascular pathologies. Despite its diagnostic potential, implementing quantitative T2 mapping at ultra-high magnetic field strengths ([&ge;]7T) poses significant challenges. These include elevated specific absorption rate (SAR) and radiofrequency (RF) field inhomogeneities, which can lead to prolonged scan durations and inaccuracies in quantification. Materials and Methods. Phase-based gradient-recalled echo (GRE) techniques have recently emerged as promising rapid acquisition with enhanced sensitivity to T2-related contrast. In this study, we introduce TWISTARE (TWo Interleaved Steady-states for T2 and RF Estimation), a novel dual steady-state 3D-GRE approach that employs interleaved flip angles and small RF phase increments to jointly estimate T2 and B1 maps. By combining two dual-steady-state scans, TWISTARE enables fast, whole-brain quantitative T2 mapping while reducing scan time and mitigating B1-related bias at ultra-high field. Results. Validation experiments included Bloch simulations, phantom studies and in-vivo imaging. The results demonstrated high precision in phantom experiments, achieving up to a two-fold reduction in acquisition time and achieved precision comparable to the gold-standard method in vivo within a similar scan duration. Discussion. TWISTARE establishes a fast steady-state framework for quantitative neuroimaging at ultrahigh field, offering potential benefits for both clinical and research applications, especially in longitudinal and dynamic studies of brain tissue.

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High-resolution advanced diffusion MRI of rectal cancer surgical specimens: correlating microstructural characteristics with histology

Fouto, A. R.; Cala, H.; Moreira, S.; Shemesh, N.; Fernandez, L.; Couto, N.; Herrando, I.; Nougaret, S.; Popita, R.; Brito, J.; Ouro, S.; Chambel, M.; Papanikolaou, N.; Parvaiz, A.; Heald, R. J.; Castillo-Martin, M.; Santiago, I.; Ianus, A.

2026-04-04 oncology 10.64898/2026.04.02.26350055 medRxiv
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Background: Despite advances in organ-preserving strategies for rectal cancer, accurate restaging after neoadjuvant therapy (NAT) remains challenging due to the limited sensitivity of conventional MRI in differentiating residual tumour from treatment-induced changes. This limitation highlights the urgent need to develop better imaging tools that can accurately analyze the complex structure of the treated rectal wall. Purpose: To study the diffusion properties of different rectal wall components, including healthy layers and pathological tissue, using high-resolution ex vivo diffusion MRI (dMRI) on whole total mesorectal excision (TME) samples obtained after NAT, and to evaluate how advanced diffusion metrics improve tissue analysis compared to standard T2-weighted imaging. Materials and Methods: Five post-NAT TME specimens were prospectively collected at a single center and fixed (36h formalin, 4h PBS). Then, specimens were mounted in Fomblin and scanned using a 9.4T Bruker BioSpec (22{degrees} ; 86 mm Tx/Rx). Diffusion MRI was acquired using a 2D multi-shell sequence (TR/TE 11,000/24 ms; 130 slices; 0.5 mm3 isotropic voxel; b = 1500 and 3000 s/mm; 15 directions) alongside multi-echo T2;-weighted imaging (TR 25,000 ms; 8 echoes; TE 10-80 ms; fat suppression). Diffusion and kurtosis parametric maps were generated by voxelwise linear least-squares fitting; T2 maps by monoexponential fitting (MATLAB). Specimens were sectioned at 5 mm, stained with H&E and dual staining (for fibrosis and smooth muscle), digitized, and co-registered with MRI using morphological landmarks. Regions-of-interest (ROIs) - mucosa, submucosa, muscle layers, tumour, and fibrous tissue - were compared using a linear mixed-effects model with FDR correction (RStudio v2025.09). Results: The muscularis propria exhibited the highest FA values of all tissue components, reflecting the ordered fiber architecture of its inner circular and outer longitudinal layers, which were visually separable on direction-encoded colour FA maps. Focal disruption of anisotropy at the tumour-muscle interface corresponded histologically to tumour invasion of the muscularis propria. Tumour regions showed the lowest mean diffusivity (MD), reflecting high cellularity and restricted diffusion, and MD was comparatively higher in the residual scar. Kurtosis metrics - particularly MK and AK - were elevated in tumour, reflecting greater microstructural heterogeneity and complexity. T2 mapping provided limited contrast across tissue types due to formalin fixation effects. Conclusion: Diffusion MRI metrics quantitatively discriminated rectal wall tissue components ex vivo with histological validation, beyond T2-weighted contrast. DTI and DKI metrics characterized tumour, fibrous tissue, and muscularis propria invasion, supporting their potential as microstructural imaging biomarkers for treatment response assessment.

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Impact of simulated MRI artifacts on deep learning-based brain age prediction

Hendriks, J.; Jansen, M. G.; Joules, R.; Pena-Nogales, O.; Elsen, F.; Povolotskaya, A.; Dijsselhof, M. B. J.; Rodrigues, P. R.; Barkhof, F.; Schrantee, A.; Mutsaerts, H.

2026-03-26 radiology and imaging 10.64898/2026.03.24.26349152 medRxiv
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Brain age is a promising biomarker for detecting atypical and pathological brain aging, but its accuracy and reliability depend critically on MRI quality. The impact of common MR image degradations such as motion, ghosting, blurring, and noise on brain age predictions remains unclear. In this study, we systematically assessed the effects of four simulated MRI artifact types, across ten severity levels, on brain age prediction using three widely used deep learning-based algorithms (Pyment, MIDI, MCCQR), in high-quality T1-weighted images of healthy adults (age range 18-85, 54% female). Artifact severity levels (1-10) were generated using a power-function mapping of TorchIO simulation parameters calibrated to the full PondrAI QC visual rating scale (from perfect to severely degraded image quality). Linear mixed-effects models with predicted brain age as dependent variable revealed a significant interaction between algorithm, artifact type, and severity (p<0.001), indicating algorithm-specific sensitivity to artifacts. In artifact-free scans, mean absolute error (MAE) was 4.6 years for MCCQR, 7.1 years for Pyment, and 9.1 years for MIDI. At severity level 10, MAE increased with up to 110% for Pyment, 112% for MCCQR, and 16% for MIDI (motion); and with up to 75% for Pyment, 135% for MCCQR, and 34% for MIDI (ghosting). Blurring had minimal impact at low-moderate levels, but at maximum severity MAE increased by 26% for Pyment and 137% for MCCQR, while MIDI remained largely stable. Noise minimally affected Pyment and MCCQR (MAE increases [&le;]20%), but led to larger declines for MIDI (MAE increase 35%). The vulnerability of different algorithms highlights that training data, preprocessing strategies and underlying architectures influence robustness, emphasizing that artifact sensitivity is a key consideration when interpreting brain-age as a biomarker. Our results emphasize the need for artifact-aware evaluation and mitigation strategies when algorithms such as brain age are used in clinical research.

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Information-Guided Parameter Optimisation for MR Elastography Radiomics

Djebbara, I.; Yin, Z.; Friismose, A. I.; Poulsen, F. R.; Hojo, E.; Aunan-Diop, J. S.

2026-03-20 radiology and imaging 10.64898/2026.03.17.26348578 medRxiv
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Mechanical properties of biological tissues vary across spatial scales, yet radiomics typically relies on fixed, heuristic choices for neighbourhood size, kernel geometry, and spectral content - choices that can silently reshape the feature space before any modelling begins. We introduce a label-free, information-theoretic framework for selecting extraction parameters in multi-frequency MRE radiomics. For each configuration {theta} - neighbourhood radius r, kernel geometry k (sphere or shell), and frequency subset f - we extract a radiomics feature matrix and score it using an objective J({theta}) that integrates distributional richness (Shannon entropy), cross-frequency coherence (canonical correlation), inter-feature redundancy (Spearman correlation), and bootstrap stability. We evaluate 121 configurations per tissue in multi-frequency MRE (30-60 Hz) of human brain, liver, and a calibrated phantom, and test robustness using 10,000 Dirichlet-sampled objective weightings. Across tissues, neighbourhood aggregation is consistently preferred over voxel-wise extraction, outperforming the no-neighbourhood baseline in 98.4-100% of weightings. External validation in 100 independent brain scans acquired with a different protocol and wider frequency range (20-90 Hz) confirms a reproducible mesoscopic plateau at r = 3-5 (9-15 mm), with a modal optimum at r = 4; omitting neighbourhood analysis reduces J({theta}) by 38% relative to each subject's optimum. Frequency-subset preferences replicate across datasets, with lower frequencies most frequently selected for brain. By turning ad hoc extraction choices into an outcome-free optimisation step, this framework improves reproducibility, reduces sensitivity to heuristic parameter choices, and generalises across acquisition protocols and imaging sites.

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Longitudinal MAP-MRI-based Assessment of Tissue Microstructural Alterations in Acute mTBI

Gangolli, M.; Perkins, N. J.; Marinelli, L.; Basser, P. J.; Avram, A. V.

2026-04-13 radiology and imaging 10.64898/2026.04.06.26350074 medRxiv
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BACKGROUNDMild traumatic brain injury (mTBI) is a signature injury in civilian and military populations that remains invisible to detection by conventional radiological methods. Diffusion MRI has been identified as a potential clinical tool for revealing subtle microstructural alterations associated with mTBI. OBJECTIVEThis study evaluates whether a comprehensive and powerful diffusion MRI (dMRI) technique called mean apparent propagator (MAP) MRI can detect sequelae of mTBI. METHODSWe analyzed data from 417 participants of the GE/NFL prospective mTBI study which included 143 matched controls (mean age, 21.9 {+/-} 8.3 years; 76 women) and 274 patients with acute mTBI and GCS [&ge;]13 (mean age, 21.9 {+/-} 8.5 years; 131 women). All participants underwent MRI exams at up to four visits including structural high-resolution T1W, T2W, FLAIR-T2W, and dMRI, in addition to clinical assessments of post-concussive physical symptoms (RPQ-3), psychosocial functioning and lifestyle symptoms (RPQ-13), and postural stability (BESS). The dMRI data for each subject were co-registered across all visits and analyzed using the MAP-MRI framework to measure and map the distribution of net microscopic displacements of diffusing water molecules in tissue and ultimately compute the microstructural MAP-MRI tissue parameters including propagator anisotropy (PA), Non-Gaussianity (NG), return-to-origin probability (RTOP), return-to-axis probability (RTAP), and return-to-plane probability (RTPP). We quantified voxel-wise and region-of-interest (ROI)-based changes in these parameters across all four visits. RESULTSMAP-MRI parameter values were within the expected ranges and showed relatively little variation across visits. We found no significant differences in the longitudinal trajectories of these parameters between mTBI patients and controls. At acute post-injury timepoints, RPQ-3 and RPQ-13 scores were increased in mTBI patients relative to controls, while BESS scores were not significantly different between groups. Analysis of dMRI metrics and clinical mTBI markers showed significant correspondence between MAP-MRI metrics in cortical gray matter, caudate and pallidum and BESS scores. CONCLUSIONWe developed and tested a state-of-the-art quantitative image processing pipeline for sensitive analysis and detection of subtle tissue changes in longitudinal clinical diffusion MRI data. The absence of a significant statistical difference between populations in the dMRI parameters in this study suggests that the mTBI corresponded to acute post-injury clinical symptoms but that the injury was not severe enough to cause detectable microstructural damage/alterations, and that increased diffusion sensitization combined with improved analysis techniques may be needed. CLINICAL IMPACTThese findings suggest that acute mTBI (GCS[&ge;]13) may not be detectable with diffusion MRI. TRIAL REGISTRATIONClinicalTrials.gov NCT02556177

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A realistic in-silico brain phantom for quantifying susceptibility anisotropy-induced error in susceptibility separation

Ridani, D.; De Leener, B.; Alonso-Ortiz, E.

2026-04-09 bioengineering 10.64898/2026.04.07.716972 medRxiv
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PurposeTo create a realistic in-silico brain phantom for positive and negative magnetic susceptibility that incorporates susceptibility anisotropy, enabling the evaluation of how susceptibility anisotropy influences susceptibility separation algorithm performance. MethodsWe expanded an existing QSM validation phantom by creating separate maps for positive and negative susceptibility, with the option of modeling susceptibility anisotropy. Multi-echo gradient echo data were simulated to evaluate four susceptibility separation techniques ({chi}-separation, DECOMPOSE-QSM, APART-QSM, and [Formula]). To assess the impact of noise, simulations were performed at different SNR levels (50, 100, 200, 300). ResultsOur findings showed that the error in negative susceptibility estimates increased by up to 53% when susceptibility anisotropy was present, compared to the case without susceptibility anisotropy, with {chi}-separation being the algorithm that was most sensitive to anisotropy. Robustness to noise varied across the assessed algorithms, with APART-QSM and {chi}-separation having the highest and lowest sensitivity to noise, respectively. ConclusionThe modified phantom is open-source and can serve as a numerical ground truth for evaluating susceptibility separation methods. Our findings emphasize the importance of incorporating susceptibility anisotropy into susceptibility separation models to improve their accuracy.

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Improving Glioblastoma Classification Using Quantitative Transport Mapping with a Synthetic Data Trained Deep Neural Network

Romano, D. J.; Roberts, A. G.; Weppner, B.; Zhang, Q.; John, M.; Hu, R.; Sisman, M.; Kovanlikaya, I.; Chiang, G. C.; Spincemaille, P.; Wang, Y.

2026-04-01 radiology and imaging 10.64898/2026.03.31.26349864 medRxiv
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Purpose: To develop a deep neural network-based, AIF-free, perfusion estimation method (QTMnet) for improved performance on glioma classification. Methods: A globally defined arterial input function (AIF) is needed to recover perfusion parameters in the two-compartment exchange model (2CXM). We have developed Quantitative Transport Mapping (QTM) to create an AIF-independent estimation method. QTM estimation can be formulated using deep neural networks trained on synthetic DCE-MRI data (QTMnet). Here, we provide a fluid mechanics-based DCE-MRI simulation with exchange between the capillaries and extravascular extracellular space. We implemented tumor ROI generation to morphologically characterize tissue perfusion. We compared our QTMnet implementation with 2CXM on 30 glioma human subjects, 15 of which had low-grade gliomas, and 15 with high-grade glioblastomas. Results: QTMnet outperforms (best AUC: 0.973) traditional 2CXM (best AUC: 0.911) in a glioma grading task. Conclusion: The AIF-independent QTMnet estimation provides a quantitative delineation between low-grade and high-grade gliomas.

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High-Field Multinuclear MRI Reveals Sodium Relaxation Heterogeneity in Cortical Organoids

Yu, G.; Liu, X.; Hike, D.; Qian, C.; Devor, A.; Zeldich, E.; Thunemann, M.; Zhou, X. A.

2026-04-05 bioengineering 10.64898/2026.04.01.715894 medRxiv
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Sodium magnetic resonance imaging (23Na MRI) provides a unique opportunity to probe ionic microenvironments in neural tissue because sodium ions play central roles in membrane electrophysiology, ion transport, and cellular homeostasis. Unlike conventional proton ({superscript 1}H) MRI, which primarily reflects water distribution and tissue structure, {superscript 2}3Na MRI is sensitive to ionic compartmentation and quadrupolar interactions arising from the spin-3/2 nature of the sodium nucleus. However, sodium MRI remains technically challenging due to intrinsically low signal sensitivity and rapid biexponential relaxation, particularly when imaging small biological systems. Here, we establish a high-field multinuclear MRI platform for imaging human cerebral organoids at 14 Tesla. Cerebral organoids derived from human induced pluripotent stem cells provide a simplified three-dimensional neural tissue model that enables investigation of ionic microenvironments without vascular or systemic confounds. Using a dual-tuned {superscript 1}H/{superscript 2}3Na radiofrequency coil, we performed co-registered structural, diffusion, and sodium imaging of individual fixed organoids. High-resolution {superscript 1}H MRI (33-100 m) revealed pronounced microstructural heterogeneity, while multi-echo {superscript 2}3Na MRI (300-400 m) enabled voxel-wise characterization of quadrupolar relaxation behavior. Bi-exponential analysis of the sodium signal decay identified distinct relaxation components (T2*short {approx} 1 ms and T2*long {approx} 12 ms) and revealed spatial heterogeneity in sodium microenvironments across the organoid tissue. These results demonstrate the feasibility of quantitative sodium relaxometry in cortical organoids and establish a multinuclear imaging platform for investigating ionic microenvironment dynamics in three-dimensional neural tissue models.

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Auxiliary Clinical Prompt Integration into Vision-Language Prompt SAM for Brain Tumor Segmentation

Hakata, Y.; Oikawa, M.; Fujisawa, S.

2026-04-17 health informatics 10.64898/2026.04.15.26351001 medRxiv
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Background. Adult diffuse glioma is a representative class of primary brain tumors for which accurate MRI-based tumor segmentation is indispensable for treatment planning. Conventional automated segmentation methods have relied primarily on image information and spatial prompts, and auxiliary clinical information that is routinely acquired in clinical practice has not been sufficiently exploited as an input. Objective. Building on a dual-prompt-driven Segment Anything Model (SAM) extension framework that fuses visual and language reference prompts, we propose a method that integrates patient demographics, unsupervised molecular cluster variables derived from TCGA high-throughput profiling, and histopathological parameters as learnable prompt embeddings, and we evaluate its effect on the accuracy of lower-grade glioma (LGG) MRI segmentation. Methods. An auxiliary prompt encoder converts clinical metadata into high-dimensional embeddings that are fused with the prompt representations of Segment Anything Model (SAM) ViT-B through a cross-attention fusion mechanism. The TCGA-LGG MRI Segmentation dataset (Kaggle release by Buda et al.; n = 110 patients; WHO grade II-III) was split at the patient level (train/val/test = 71/17/22) using three different random seeds, and the three slices with the largest tumor area were extracted from each patient. To avoid pseudo-replication arising from multiple slices per patient and repeated measurements across seeds, our primary analysis aggregated Dice and 95th-percentile Hausdorff distance (HD95) to the patient x seed unit (n = 66); secondary analyses at the unique-patient level (n = 22) and at the per-slice level (n = 198) are also reported. Pairwise comparisons used paired t-tests with Bonferroni correction (k = 3) and Wilcoxon signed-rank tests, and a permutation test (K = 30) served as an auxiliary check of effective use of the auxiliary information. Results. At the patient x seed level (n = 66), Proposed (full clinical) achieved a Dice gain of +0.287 over the zero-shot SAM ViT-B baseline (paired-t p = 4.2 x 10^-15, Cohen's d_z = +1.25, Bonferroni-corrected p << 0.001; Wilcoxon p = 2.0 x 10^-10), and HD95 improved from 218.2 to 64.6. Because zero-shot SAM is not designed for domain-specific medical segmentation, the large absolute HD95 gap largely reflects the expected domain gap rather than a competitive baseline. The additional contribution of the full clinical configuration over the demographics-only configuration was Dice = +0.023 (paired-t p = 0.057, Bonferroni-corrected p = 0.172), which did not reach statistical significance at the patient level and is reported as a directional trend. The permutation test (K = 30, seed 2025) yielded real-metadata Dice = 0.819 versus a shuffled-metadata mean of 0.773, giving an empirical p = 0.032 = 1/(K + 1), which is at the resolution limit of this test and should therefore be interpreted as preliminary evidence. Conclusions. Integrating auxiliary clinical information as multimodal prompts produced a large improvement over the zero-shot SAM baseline on this LGG cohort. More importantly, a robustness analysis showed that Proposed (full clinical) outperformed the trained Base (no auxiliary information) under all tested spatial-prompt conditions, including perfect centroid (+0.014), and that the advantage was most pronounced in the prompt-free regime (+0.231, p = 0.039), where the base model collapsed but the proposed model maintained meaningful segmentation by leveraging clinical metadata alone. The additional contribution of molecular and histopathological information beyond demographics was not statistically resolved at the patient level (+0.023, n.s.). Establishing clinical utility will require external validation on larger multi-center cohorts and direct comparisons with established segmentation methods. Keywords: brain tumor segmentation; Segment Anything Model (SAM); vision-language prompt-driven segmentation; auxiliary clinical prompts; multimodal learning; TCGA-LGG; deep learning

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Probabilistic Cerebral Blood Flow Trajectories Across the Adult Lifespan Using Quantitative Water PET

Johansson, J.; Palonen, S.; Egorova, K.; Tuisku, J.; Harju, H.; Kärpijoki, H.; Maaniitty, T.; Saraste, A.; Saari, T.; Tuomola, N.; Rinne, J.; Nuutila, P.; Latva-Rasku, A.; Virtanen, K. A.; Knuuti, J.; Nummenmaa, L.

2026-04-11 radiology and imaging 10.64898/2026.04.08.26350393 medRxiv
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BackgroundQuantitative cerebral blood flow (CBF) measured with [15O]water positron emission tomography (PET) is the reference standard for quantifying brain perfusion. However, clinical interpretation of individual CBF measurements is limited by the absence of large normative datasets accounting for physiological variability across the adult lifespan. Long-axial field-of-view PET enables high-sensitivity quantitative [15O]water perfusion imaging without arterial blood sampling, allowing normative characterization of cerebral perfusion at unprecedented scale. The aim of this study was to establish normative and covariate-adjusted models of cerebral blood flow across the adult lifespan using total-body [15O]water PET. MethodsQuantitative CBF measurements were obtained in 302 neurologically healthy adults (age 21-86 years) using total-body [15O]water PET. Linear mixed-effects models were used to evaluate the effects of age, sex, body mass index (BMI), and blood hemoglobin concentration on CBF and to generate normative prediction models across the adult lifespan. Between-subject and within-subject variability were estimated from repeated scans in a subset of participants (n=51). ResultsMean grey matter CBF was 46.1 mL/(min*dL), with substantial inter-individual variability but high within-subject reproducibility (intraclass correlation coefficients 0.78-0.89). Advancing age was associated with a decline in CBF of approximately 7% per decade (p_FDR < 10-12). Higher BMI was associated with lower CBF (approximately -6% per 10 kg/m2; p_FDR < 0.01). Women exhibited higher CBF than men (approximately 7.5%), but this difference was largely explained by lower blood hemoglobin concentration in women. Covariate-adjusted models were used to generate normative predictions and prediction intervals describing expected CBF across adulthood. ConclusionThis study establishes a normative database of quantitative cerebral blood flow across the adult lifespan using high-sensitivity [15O]water PET. Age, BMI, and hemoglobin are major determinants of inter-individual variability in CBF. The resulting generative models provide a quantitative reference framework for interpreting cerebral perfusion measurements and may enable automated detection of abnormal brain perfusion in clinical PET imaging.

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Multi-Contrast MRI Inputs Enable Self-Consistent Tissue Segmentation & Robust Perivascular Space Identification

Gunter, J. L.; Preboske, G. M.; Persons, B.; Przybelski, S. A.; Schwarz, C. G.; Low, A.; Vemuri, P.; Petersen, R.; Jack, C. R.

2026-04-07 neuroscience 10.64898/2026.04.03.716409 medRxiv
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Different MRI image contrasts are designed to highlight various tissue properties and combining them allows extension of probabilistic segmentation beyond the commonly used "gray-white-CSF" models. This work describes a fully automated method that combines T1-weighted, T2-FLAIR, and conventional T2-weighted images to provide internal consistency across prediction of tissue segmentations including segmentation of superficial and deep gray matter, white matter hyperintensities, and MR-visible perivascular spaces. Results from 773 imaging datasets from 403 participants in the Mayo Clinic Study of Aging and Mayo Clinic Alzheimers Disease Research Center (ADRC) are presented.

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Feasibility of Volumetric Analysis using Bedside Ultra-Low-Field Portable Magnetic Resonance Imaging in Patients receiving Extracorporeal Membrane Oxygenation

Stockbridge, M. D.; Faria, A. V.; Neal, V.; Diaz-Carr, I.; Soule, Z.; Ahmad, Y. B.; Khanduja, S.; Whitman, G.; Hillis, A. E.; Cho, S.-M.

2026-04-13 neurology 10.64898/2026.04.09.26350481 medRxiv
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The SAFE MRI ECMO (NCT05469139) study established the safety of ultra-low-field 64mT MRI in patients receiving extracorporeal membrane oxygenation (ECMO) in the setting of intensive care and demonstrated that these images were highly sensitive in detecting acquired brain injuries. This retrospective analysis of prospectively collected observational data sought to expand on these findings in light of the crucial need for neurological monitoring while patients receive ECMO by evaluating the feasibility of volumetric analyses derived from ultra-low-field MR images. T2-weighted scans from thirty patients who received ultra-low-field MRI while undergoing ECMO at Johns Hopkins Hospital were analyzed using a volumetric pipeline to determine whole brain volume and volumes of total grey matter, total white matter, subcortical grey matter, ventricles, left hemisphere, right hemisphere, telencephalon, left and right lateral ventricles, the total intracranial volume, and the cerebellum. Segmented brain volumes in patients undergoing ECMO were comparable to measurements obtained using conventional field and ultra-low-field MRI in the absence of ECMO instrumentation. The subgroup analysis demonstrated subtle volumetric differences between patients supported with venoarterial ECMO and those receiving venovenous ECMO. These data provide the first evidence that ultra-low-field MRI provides volumetric measurements comparable to conventional field-strength MRI, even in the presence of ECMO circuitry, supporting its feasibility for neuroimaging in critically ill patients.

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PINK1 Expression as a Prognostic Biomarker in Glioblastoma Multiforme: An Observational Multicenter Study

Garcia Rairan, L. A.; Corpus Gutierrez, v.; Del castillo, m. a.; Riveros Castillo, W.; Saavedra Gerena, J.; Turizo Smith, A. D.; Arias Guatibonza, J.

2026-04-05 oncology 10.64898/2026.04.03.26350127 medRxiv
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Introduction: Glioblastoma multiforme (GBM) remains the most lethal primary brain tumor with median survival of 14-15 months. Current prognostic markers inadequately stratify patient outcomes. PINK1 (PTEN-induced putative kinase 1), a mitochondrial kinase regulating mitophagy and cellular stress responses, has emerged as a promising prognostic candidate. Our preliminary analysis of 20 GBM cases demonstrated significant PINK1 expression with correlation to aggressive phenotypes (Turizo Smith et al., 2025). This multicenter study aims to prospectively validate PINK1 as a prognostic biomarker for survival and functional outcomes in a Latin American cohort. Methods and analysis: PINK1-GBM Colombia is a multicenter, observational cohort study across four tertiary hospitals in Bogota, Colombia (Hospital de Kennedy, Hospital El Tunal, Hospital Santa Clara and Hospital Universitario de la Samaritana). We will enroll at least 26-50 adults (18+ years) with newly diagnosed IDH-wild type GBM undergoing surgical resection. PINK1 expression will be quantified by immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue using standardized protocols. Primary outcomes: overall survival (OS) and progression-free survival (PFS). Secondary outcomes: functional status trajectories (KPS/ECOG). Follow-up extends 24 months with clinical, imaging (RANO 2.0), and telephone assessments. Survival analyses will employ Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models adjusted for established prognostic factors. Ethics and dissemination: Approved by Universidad Nacional de Colombia Ethics Committee (Acta 001, February 5, 2026; Ref: 2.FM.1.002-CE-002-26), Subred Sur Occidente (P-AP-19-2025, July 11, 2025), and Subred Centro Oriente (CEI 067/2025, October 24, 2025). Conducted per Declaration of Helsinki and Colombian Resolution 8430/1993. Results will be disseminated via peer-reviewed publication, international conferences, and thesis submission.

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Imaging solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy human participants

Wen, X.; Sun, Y.; Zhou, X.; Li, Y.; Paez, A.; Varghese, J.; Pillai, J. J.; Knutsson, L.; Van Zijl, P. C. M.; Leigh, R.; Kamson, D. O.; Graley, C. R.; Saidha, S.; Bakker, A.; Ward, B. K.; Kashani, A. H.; Hua, J.

2026-04-08 radiology and imaging 10.64898/2026.04.03.26349283 medRxiv
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Background: Recently, a posterior pathway for fluid drainage from the retina to the meningeal lymphatics in the optic nerve (ON) sheath was identified in rodents using intravitreal imaging tracers directly injected into the ocular-globe. Fluid and solute clearance along this pathway may be associated with many diseases. However, intravitreal tracers are rarely used in clinical imaging. As intravenous Gadolinium-based-contrast-agent (GBCA) can enter the globe via the blood-ocular-barriers, it may provide an alternative approach to image this pathway. Purpose: To establish a clinically feasible intravenous GBCA-based MRI approach for tracking fluid and solute transport along the posterior lymphatic pathway in the ocular glymphatic system. Materials & Methods: This prospective study was conducted from March 2021 to September 2022 in healthy participants. Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was performed before, immediately and 4 hours after intravenous-GBCA administration to track GBCA distribution in aqueous humor (AH) and cerebrospinal fluid (CSF) in regions-of-interest (ROIs) in the globe (anterior-cavity, vitreous-body), in the intraorbital and extraorbital ON, and in the intracranial CSF space proximal to the ON (chiasmatic-cistern, interpeduncular-cistern). Kruskal-Wallis tests with post-hoc Dunn's tests were used for group comparisons. Results: Sixteen healthy participants (mean age +/- SD: 51 +/- 21 years, 5 men) were recruited. Intravenous-GBCA enhancement was observed in all ROIs immediately after injection. At 4-hour-post-GBCA, the vitreous body showed a trend of smaller enhancement area (55 +/- 11% versus 49 +/- 11%, P=.14) and lower GBCA-concentration (0.044 +/- 0.014 versus 0.028 +/- 0.010 mmol/L, P=.07) compared to immediate-post-GBCA. The intraorbital ON showed more widespread enhancement (39 +/- 5% versus 59 +/- 6%, P=.01) and significantly higher GBCA-concentration (0.023 +/- 0.009 versus 0.059 +/- 0.015 mmol/L, P<.001) at 4-hour-post-GBCA. Conclusion: Dynamic fluid and solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy participants was measured by tracking intravenous-GBCAs entering the globe via the blood-ocular-barriers using cDSC-MRI.

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HybridNet-XR: Efficient Teacher-Free Self-Supervised Learning for Autonomous Medical Diagnostic Systems in Resource-Constrained Environments.

Mayala, S.; Mzurikwao, D.; Suluba, E.

2026-03-19 health informatics 10.64898/2026.03.16.26348570 medRxiv
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Deep learning model classification on large datasets is often limited in countries with restricted computational resources. While transfer learning can offset these limitations, standard architectures often maintain a high memory footprint. This study introduces HybridNet-XR, a memory-efficient and computationally lightweight hybrid convolutional neural network (CNN) designed to bridge the domain gap in medical radiography using autonomous self-supervised learning protocols. The HybridNet-XR architecture integrates depthwise separable convolutions for parameter reduction, residual connections for gradient stability, and aggressive early downsampling to minimize the video RAM (VRAM) footprint. We evaluated several training paradigms, including teacher-free self-supervised learning (SSL-SimCLR), teacher-led knowledge distillation (KD), and domain-gap (DG) adaptation. Each variant was pre-trained on ImageNet-1k subsets and fine-tuned on the ChestX6 multi-class dataset. Model interpretability was validated through gradient-weighted class activation mapping (Grad-CAM). The performance frontier analysis identified the HybridNet-XR-150-PW (Pre-warmed) as the optimal configuration, achieving a 93.38% average accuracy and 99% AUC while utilizing only 814.80 MB of VRAM. Regarding class-wise accuracy, this variant significantly outperformed standard MobileNetV2 and teacher-led models in critical diagnostic categories, notably Covid-19 (97.98%) and Emphysema (96.80%). Grad-CAM visualizations confirmed that the teacher-free pre-warming phase allows the model to develop sharper, anatomically grounded focus on pathological landmarks compared to distilled models. Specialized pre-warming schedules offer a viable, computationally autonomous alternative to knowledge distillation for medical imaging. By eliminating the requirement for high-performance teacher models, HybridNet-XR provides a robust and trustworthy diagnostic foundation suitable for clinical deployment in resource-constrained environments. Author summaryTraditional deep learning models for medical imaging are often too large for the low-power computers available in many global health settings. We developed a new model to bridge this computational gap. We designed HybridNet-XR, a highly efficient AI architecture, and trained it using a "teacher-free" method that doesnt require a massive supercomputer. We found a specific version (H-XR150-PW) that provides high accuracy while using very little memory. Our results show that high-performance diagnostic AI can be deployed on standard, low-cost hardware. Furthermore, using visual heatmaps (Grad-CAM), we proved that the AI correctly identifies medical landmarks like lung opacities, ensuring it is safe and reliable for real-world clinical use.

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VIsual STAndardized Quantification of LGE (VISTAQ), a contour-less method for late gadolinium enhancement quantification

Aquaro, G. D.; Licordari, R.; De Gori, C.; Todiere, G.; Ianni, U.; Barison, A.; De Luca, A.; Folgheraiter, a.; Grigoratos, C.; alberti, m.; lombardo, m.; De Caterina, R.; Sinagra, G.; Emdin, M.; Di Bella, G.; fulceri, l.

2026-04-15 cardiovascular medicine 10.64898/2026.04.09.26350552 medRxiv
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Background: Late gadolinium enhancement (LGE) quantification by cardiovascular magnetic resonance is central to risk stratification in hypertrophic cardiomyopathy (HCM), yet conventional techniques require contour tracing and region-of-interest (ROI) placement, which may reduce reproducibility and increase analysis time. We developed a novel visual standardized approach, the Visual Standardized Quantification of LGE (VISTAQ), that does not require myocardial contouring, arbitrary ROI positioning, or dedicated post-processing software. Methods: In this multicenter, multivendor retrospective study, LGE images from 400 patients (100 prior myocardial infarction, 250 HCM, 50 other non-ischemic heart diseases) were analyzed. VISTAQ subdivides each myocardial segment into transmural mini-segments and classifies LGE visually using predefined criteria, expressing global LGE burden as the percentage of positive mini-segments. Reproducibility was assessed in 250 patients across different observer expertise levels using intraclass correlation coefficients (ICC) and Bland?Altman analysis. In 100 HCM patients, VISTAQ was compared with conventional methods (mean+2SD, +5SD, +6SD, FWHM, visual thresholding). Prognostic performance was evaluated in 250 HCM patients over a median 5-year follow-up. Results: VISTAQ demonstrated excellent intra- and inter-observer reproducibility (ICC up to 0.98 and 0.97, respectively), consistent across disease subtypes. Compared with conventional techniques, VISTAQ showed similar ICC to FWHM but significantly lower net and absolute inter-observer differences (median absolute difference 1.3%). Mean+2SD markedly overestimated LGE, whereas mean+6SD slightly underestimated LGE compared with VISTAQ, mean+5SD, FWHM, and visual thresholding. Analysis time was substantially shorter with VISTAQ (median 105 vs. 375 seconds, p<0.0001). During follow-up, 21 hard cardiac events occurred in HCM population. An LGE threshold >10% predicted events with higher accuracy using VISTAQ (AUC 0.90; sensitivity 85%; specificity 94%) compared with mean+6SD (AUC 0.75; sensitivity 57%; specificity 93%). Conclusions: VISTAQ provides highly reproducible, time-efficient LGE quantification without dedicated software and demonstrates non-inferior prognostic discrimination in HCM compared with conventional threshold-based techniques.

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CorSeg-CineSAX: An Open-Source Deep Learning Framework for Fully Automatic Segmentation of Short-Axis Cine Cardiac MRI Across Multiple Cardiac Diseases

Xu, R.; Jiang, S.; Zhai, Y.; Chen, Y.

2026-04-03 cardiovascular medicine 10.64898/2026.04.01.26349955 medRxiv
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Background: Segmentation of the left ventricular myocardium, left ventricular cavity, and right ventricular cavity on short-axis cine cardiac magnetic resonance (CMR) images is essential for quantifying cardiac structure and function. However, existing automated segmentation tools are limited by small training datasets, narrow disease coverage, restrictive input format requirements, and the absence of anatomical plausibility constraints, hindering their clinical adoption. Methods: We constructed the largest annotated CMR short-axis segmentation dataset to date, comprising 1,555 subjects from 12 centers with five cardiac disease types and full cardiac cycle annotations totaling 319,175 labeled images. A MedNeXt-L model was trained using a 2D slice-by-slice strategy with full field-of-view input, eliminating dependencies on 3D volumes, temporal sequences, or region-of-interest(ROI) localization. A deterministic three-step post-processing pipeline was designed to enforce anatomical priors: connected component constraint, containment relationship constraint, and gap-filling constraint. The model was validated on an internal test set (310 subjects) and three independent public external datasets (ACDC, M&Ms1, M and Ms2; 855 subjects from 6 additional centers across 3 countries), spanning 15 cardiac disease categories-10 of which were never encountered during training. Results: The model achieved mean Dice similarity coefficients (DSC) of 0.913 {+/-} 0.037 and 0.911 {+/-} 0.040 on internal and external test sets, respectively, with a cross-domain performance gap of only 0.002. Post-processing eliminated all containment violations (7.5% [-&gt;] 0%) and gap errors (1.8% [-&gt;] 0%) while reducing fragment rates by 85.5% (9.0% [-&gt;] 1.3%). Zero-shot generalization to 10 unseen disease categories yielded DSC values ranging from 0.899 to 0.921. Automated clinical functional parameters demonstrated excellent agreement with manual measurements for left ventricular indices and right ventricular volumes (intraclass correlation coefficients [&ge;] 0.977). Conclusions: CorSeg-CineSAX provides a robust, open-source framework for fully automatic CMR short-axis segmentation across diverse clinical scenarios. All source code and pre-trained weights are publicly available at https://github.com/RunhaoXu2003/CorSeg.