Functional Imaging Research Articles

Improving source estimation of retinotopic MEG responses by combining data from multiple subjects

Abstract Magnetoencephalography (MEG) is a functional brain imaging modality, which measures the weak magnetic field arising from neuronal activity. The source amplitudes and locations are estimated from the sensor data by solving an ill-posed inverse problem. Commonly used solutions for these problems operate on data from individual subjects. Combining the measurements of multiple subjects has been suggested to increase the spatial resolution of MEG by leveraging the intersubject differences for increased information. In this article, we compare 3 multisubject analysis methods on a retinotopic mapping dataset recorded from 20 subjects. The compared methods are eLORETA with source-space averaging, minimum Wasserstein estimates (MWE), and MWE with source-space averaging. The results were quantified by the geodesic distances between early (60–100 ms) MEG peak activations and fMRI-based retinotopic target points in the primary visual cortex (V1). By increasing the subject count from 1 to 10, the median distances decreased by 6.6–9.4 mm (33–46%) compared with the single-subject median distances of around 20 mm. The observed peak activation locations with multisubject analysis also comply better with the established retinotopic maps of the primary visual cortex. Our results suggest that higher spatial accuracy can be achieved by pooling data from multiple subjects. The strength of MWE lies in individualized and sparse source estimates, but in our data, averaging eLORETA estimates across individuals in source space outperformed MWE in spatial accuracy.

Functional near-infrared spectroscopy and language development: An integrative review.

Functional near-infrared spectroscopy (fNIRS) stands poised to revolutionize our understanding of auditory detection, speech perception, and language development in infants. In this study, we conducted a meticulous integrative review across Medline, Scopus, and LILACS databases, targeting investigations utilizing fNIRS to explore language-related features and cortical activation during auditory stimuli in typical infants. We included studies that used the NIRS technique to study language and cortical activation in response to auditory stimuli in typical infants between 0 and 3years old. We used the ROBINS-I tool to assess the quality and the risk of bias in the studies. Our analysis, encompassing 66 manuscripts, is presented in standardized tables for streamlined data extraction. We meticulously correlated findings with children's developmental stages, delineating crucial insights into brain development and its intricate interplay with language outcomes. Although most studies have a high risk for overall bias, especially due to the high loss of data in NIRS studies, the low risk in the other domains is predominant and homogeneous among the studies. Highlighted are the unique advantages of fNIRS for pediatric studies, underscored by its innate suitability for use in children. This review accentuates fNIRS' capacity to elucidate the neural correlates of language processing and the sequential steps of language acquisition. From birth, infants exhibit abilities that lay the foundation for language development. The progression from diffuse to specific neural activation patterns is extremely influenced by exposure to languages, social interaction, and prosodic features and, reflects the maturation of brain networks involved in language processing. In conclusion, fNIRS emerges as an indispensable functional imaging modality, providing insights into the temporal dynamics of language acquisition and associated developmental milestones. This synthesis presents the pivotal role of fNIRS in advancing our comprehension of early language development and paves the way for future research endeavors in this domain.

Advanced Neural Functional Imaging in C. elegans Using Lab-on-a-Chip Technology.

The ability to perceive and adapt to environmental changes is crucial for the survival of all organisms. Neural functional imaging, particularly in model organisms, such as Caenorhabditis elegans, provides valuable insights into how animals sense and process external cues through their nervous systems. Because of its fully mapped neural anatomy, transparent body, and genetic tractability, C. elegans serves as an ideal model for these studies. This review focuses on advanced methods for neural functional imaging in C. elegans, highlighting calcium imaging techniques, lab-on-a-chip technologies, and their applications in the study of various sensory modalities, including chemosensation, mechanosensation, thermosensation, photosensation, and magnetosensation. We discuss the benefits of these methods in terms of precision, reproducibility, and ability to study dynamic neural processes in real time, ultimately advancing our understanding of the fundamental principles of neural activity and connectivity.

Phase-Resolved Functional Lung MRI for Pulmonary Ventilation and Perfusion (V/Q) Assessment.

Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time series of each voxel is analyzed with regard to the cardiac and breathing frequency components. Using a standard 2D spoiled gradient-echo sequence with a temporal resolution of ~300 ms, an image-sorting algorithm was developed to produce phase-resolved functional lung imaging (PREFUL) with an increased temporal resolution. Thus, it is feasible to evaluate regional flow volume loops (FVL) during tidal volume breathing and depict the propagation of the pulse wave during the cardiac cycle. This method can be applied at 1.5T or 3T with standard MR hardware without the necessity for sequence programming, as the described protocol can be implemented with the default SPGRE sequence on most systems. PREFUL ventilation MRI has been validated using 129Xe and 19F gas imaging with good regional agreement. Perfusion-weighted PREFUL MRI has been validated using SPECT as well as dynamic contrast enhanced (DCE) MRI. PREFUL has been tested in a dual center dual vendor setting and is currently applied in several ongoing multicenter trials. Furthermore, it is feasible across a range of field strengths (0.55T-3T) and different age groups, including newborns. Quantitative V/Q PREFUL MRI has been used in patients with cystic fibrosis, chronic obstructive pulmonary disease, chronic thromboembolic pulmonary hypertension, and corona virus disease-2019 to quantify disease and monitor treatment change after therapy. Furthermore, PREFUL V/Q imaging has been shown to predict transplant loss due to chronic lung allograft dysfunction in patients after lung transplantation. In summary, PREFUL MRI is a validated technique for quantitative ventilation and pulmonary pulse wave/perfusion imaging for regional pulmonary disease detection, quantification, and treatment monitoring with potential added value to the current clinical routine.

(Invited) Sub-Particle-Resolution Microscopy Reveals Inter-Facet Junction Effects on Particulate Photoelectrodes

This presentation will describe our recent work in using single-particle/single-molecule imaging approaches to study photoelectrocatalytic properties of particulate semiconductor photocatalysts, important for many solar energy conversion technologies. In anisotropically shaped photocatalyst particles, the different constituent facets differ in their electronic and thus photoelectrocatalytic properties, and between different facets they may form inter-facet junctions at their adjoining edges, analogous to lateral two-dimensional (2D) heterojunctions or pseudo-2D junctions made of few-layer 2D materials. Using subfacet-level multimodal functional imaging, we uncover inter-facet junction effects on anisotropically shaped bismuth vanadate (BiVO4) particles and identify the characteristics of near-edge transition zones on the particle surface, which underpin the whole-particle photoelectrochemistry. The imaging tools, the analytical framework and the inter-facet junction concept pave new avenues towards understanding, predicting and engineering (opto)electronic and photoelectrochemical properties of faceted semiconducting materials, with broad implications in energy science and semiconductor technology.

Revolutionizing Cardiac Imaging: A Scoping Review of Artificial Intelligence in Echocardiography, CTA, and Cardiac MRI.

Cardiac imaging is crucial for diagnosing heart disorders. Methods like X-rays, ultrasounds, CT scans, and MRIs provide detailed anatomical and functional heart images. AI can enhance these imaging techniques with its advanced learning capabilities. In this scoping review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) Guidelines, we searched PubMed, Scopus, Web of Science, and Google Scholar using related keywords on 16 April 2024. From 3679 articles, we first screened titles and abstracts based on the initial inclusion criteria and then screened the full texts. The authors made the final selections collaboratively. The PRISMA chart shows that 3516 articles were initially selected for evaluation after removing duplicates. Upon reviewing titles, abstracts, and quality, 24 articles were deemed eligible for the review. The findings indicate that AI enhances image quality, speeds up imaging processes, and reduces radiation exposure with sensitivity and specificity comparable to or exceeding those of qualified radiologists or cardiologists. Further research is needed to assess AI's applicability in various types of cardiac imaging, especially in rural hospitals where access to medical doctors is limited. AI improves image quality, reduces human errors and radiation exposure, and can predict cardiac events with acceptable sensitivity and specificity.

Associations of alcohol and tobacco use with psychotic, depressive and developmental disorders revealed via multimodal neuroimaging

People affected by psychotic, depressive and developmental disorders are at a higher risk for alcohol and tobacco use. However, the further associations between alcohol/tobacco use and symptoms/cognition in these disorders remain unexplored. We identified multimodal brain networks involving alcohol use (n = 707) and tobacco use (n = 281) via supervised multimodal fusion and evaluated if these networks affected symptoms and cognition in people with psychotic (schizophrenia/schizoaffective disorder/bipolar, n = 178/134/143), depressive (major depressive disorder, n = 260) and developmental (autism spectrum disorder/attention deficit hyperactivity disorder, n = 421/346) disorders. Alcohol and tobacco use scores were used as references to guide functional and structural imaging fusion to identify alcohol/tobacco use associated multimodal patterns. Correlation analyses between the extracted brain features and symptoms or cognition were performed to evaluate the relationships between alcohol/tobacco use with symptoms/cognition in 6 psychiatric disorders. Results showed that (1) the default mode network (DMN) and salience network (SN) were associated with alcohol use, whereas the DMN and fronto-limbic network (FLN) were associated with tobacco use; (2) the DMN and fronto-basal ganglia (FBG) related to alcohol/tobacco use were correlated with symptom and cognition in psychosis; (3) the middle temporal cortex related to alcohol/tobacco use was associated with cognition in depression; (4) the DMN related to alcohol/tobacco use was related to symptom, whereas the SN and limbic system (LB) were related to cognition in developmental disorders. In summary, alcohol and tobacco use were associated with structural and functional abnormalities in DMN, SN and FLN and had significant associations with cognition and symptoms in psychotic, depressive and developmental disorders likely via different brain networks. Further understanding of these relationships may assist clinicians in the development of future approaches to improve symptoms and cognition among psychotic, depressive and developmental disorders.

Constraint Induced Movement Therapy Confers only a Transient Behavioral Benefit but Enduring Functional Circuit-Level Changes after Experimental TBI.

Although the behavioral outcome of Constraint-Induced Movement Therapy (CIMT) is well known, and that a combination of CIMT and arm use training potentiates the effect, there has been limited study of the brain circuits involved that respond to therapy. An understanding of CIMT from a brain network level would be useful for guiding the duration of effective therapy, the type of training regime to potentiate the outcome, as well as brain regional targets that might be amenable for direct neuromodulation. Here we investigated the effect of CIMT therapy alone unconfounded by additional rehabilitation training in order to determine the impact of intervention at the circuit level. Adult rats were injured by controlled cortical impact injury and studied before and then after 2wks of CIMT or noCIMT at 1-3wks post-injury using a combination of forelimb behavioral tasks and task-based and resting state functional magnetic resonance imaging at 3 and 7wks post-injury and compared to sham rats. There was no difference in behavior or functional imaging between CIMT and noCIMT after injury before intervention so that data are unlikely to be confounded by differences in injury severity. CIMT produced only a transient reduction in limb deficits compared to noCIMT immediately after the intervention, but no difference thereafter. However, CIMT resulted in a persistent reduction in contralesional limb-evoked activation and a corresponding ipsilesional cortical plasticity compared to noCIMT that endured 4wks after intervention. This was associated with a significant amelioration of intra and inter-hemispheric connectivity present in the noCIMT group at 7wks post-injury.

A head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MR in patients with nasopharyngeal carcinoma under different disease settings.

Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) are complementary in staging of nasopharyngeal carcinoma (NPC). The combination of MRI and functional imaging from PET in PET/MR is promising in NPC management. Diagnostic performance of PET/CT and PET/MR was compared in 46 patients with histologically confirmed NPC under different disease scenarios, including primary non-metastatic cases, primary metastatic cases, recurrence and/or metastasis after treatment, and post-treatment follow-up cases. Forty-six patients underwent both PET/CT and PET/MR in the same day. Primary tumor extension into risk-stratified anatomic structures, retropharyngeal and cervical lymph node metastasis, distant metastasis and post-treatment follow-up results, were compared. For high-risk structures, PET/MR detected two more sides of tensor/levator veli palatine muscle involvement, one more case of clivus involvement, and ruled out 12 false-positive sides of prevertebral muscle involvement by PET/CT. For medium-risk structures, PET/MR detected four more sides of medial pterygoid muscle involvement. For low-risk structures, abnormal signal on massa lateralis atlantis was detected by PET/MR. PET/MR detected 14 more positive retropharyngeal lymph nodes and more liver micrometastases than PET/CT. Overall, PET/MR changed two patients' T staging. Positron emission tomography/MR outperforms PET/CT in delineating muscle, skull-base bone, and nodal involvement, and identifying liver micrometastases, may serve as a single-step staging modality for NPC.

Moving beyond processing- and analysis-related variation in resting-state functional brain imaging.

When fields lack consensus standard methods and accessible ground truths, reproducibility can be more of an ideal than a reality. Such has been the case for functional neuroimaging, where there exists a sprawling space of tools and processing pipelines. We provide a critical evaluation of the impact of differences across five independently developed minimal preprocessing pipelines for functional magnetic resonance imaging. We show that, even when handling identical data, interpipeline agreement was only moderate, critically shedding light on a factor that limits cross-study reproducibility. We show that low interpipeline agreement can go unrecognized until the reliability of the underlying data is high, which is increasingly the case as the field progresses. Crucially we show that, when interpipeline agreement is compromised, so too is the consistency of insights from brain-wide association studies. We highlight the importance of comparing analytic configurations, because both widely discussed and commonly overlooked decisions can lead to marked variation.

Motor somatotopy impacts imagery strategy success in human intracortical brain-computer interfaces.

The notion of a somatotopically organized motor cortex, with movements of different body parts being controlled by spatially distinct areas of cortex, is well known. However, recent studies have challenged this notion and suggested a more distributed representation of movement control. This shift in perspective has significant implications, particularly when considering the implantation location of electrode arrays for intracortical brain-computer interfaces (iBCIs). We sought to evaluate whether the location of neural recordings from the precentral gyrus, and thus the underlying somatotopy, has any impact on the imagery strategies that can enable successful iBCI control. Three individuals with a spinal cord injury were enrolled in an ongoing clinical trial of an iBCI. Participants had two intracortical microelectrode arrays implanted in the arm and/or hand areas of the precentral gyrus based on presurgical functional imaging. Neural data were recorded while participants attempted to perform movements of the hand, wrist, elbow, and shoulder. We found that electrode arrays that were located more medially recorded significantly more activity during attempted proximal arm movements (elbow, shoulder) than did lateral arrays, which captured more activity related to attempted distal arm movements (hand, wrist). We also evaluated the relative contribution from the two arrays implanted in each participant to decoding accuracy during calibration of an iBCI decoder for translation and grasping tasks. For both task types, imagery strategy (e.g., reaching vs. wrist movements) had a significant impact on the relative contributions of each array to decoding. Overall, we found some evidence of broad tuning to arm and hand movements; however, there was a clear bias in the amount of information accessible about each movement type in spatially distinct areas of cortex. These results demonstrate that classical concepts of somatotopy can have real consequences for iBCI use, and highlight the importance of considering somatotopy when planning iBCI implantation.

Abstract Mo085: Direct effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cardiomyocyte function as a potential therapy for Phospholamban cardiomyopathy

Introduction: Phospholamban (PLN) cardiomyopathy is a dilated and arrhythmogenic cardiomyopathy caused by a single deletion of arginine in PLN gene (PLN-R14del). Clinically, It presents with heart failure, ventricular arrhythmias and sudden cardiac death, and there is still no effective and/or specific treatment besides the heart transplant. Hypothesis: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown cardiovascular outcomes improvement in general heart failure patients in multiple clinical trials. We hypothesize that SGLT2 inhibitors could ameliorate the contractile dysfunction in PLN cardiomyopathy. Goals: Identify whether there is a direct cardiac effect of SGLT2 inhibitors on PLN cardiomyopathy. Approach: We used a human iPSC-derived cardiomyocyte (hiPSC-CMs) model of PLN cardiomyopathy that mimics the impaired contractility of the disease to evaluate the contractile function after 4 days of Empagliflozin treatment by using functional cellular imaging assays. Additionally, we evaluated the effect of Empagliflozin treatment on CaMKII phosphorylation and activation of apoptosis mediators by measuring protein expression. All the experiments were compared to results using a CRISPR-engineered isogenic (healthy) line control hiPSC-CMs. Results: 4 days of Empagliflozin treatment significantly restored contractile function, decreased levels of CaMKII phosphorylation, and decreased apoptotic activity in hiPSC-CMs with PLN cardiomyopathy when compared to their healthy (isogenic) control. Conclusions: Our study provided evidence that SGLT2 inhibitors might serve as a therapeutic strategy to ameliorate contractile dysfunction and suppress arrhythmia in PLN cardiomyopathy.

Lipid-Lowering Medication and Outcomes After Anatomical and Functional Imaging in Suspected Coronary Artery Disease.

Anatomical and functional imaging identify different phenotypes of coronary artery disease (CAD) that may have implications for lipid-lowering medication (LLM). The aim of this study was to assess the associations between LLM and long-term outcomes after combined anatomical and functional imaging in patients with suspected obstructive CAD. Consecutive patients (n=1,973; 41% men; median age: 63 years) underwent coronary computed tomography angiography (CTA) because of suspected CAD. Patients in whom obstructive CAD was not ruled out by CTA underwent ischemia testing by positron emission tomography. Data on LLM purchases were collected until 2 years, and the combined endpoints of death, myocardial infarction, and unstable angina pectoris were assessed at a median of 6.7 years. After imaging, LLM was used by 24% of patients with no CAD, 51% of patients with nonobstructive CAD, 72% of patients with obstructive CAD on CTA without myocardial ischemia, and 91% of patients with myocardial ischemia. The use of LLM decreased during follow-up, with 77% of patients with myocardial ischemia using LLM for 2 years. The use ofLLM was associated with a lower annual rate of adverse events in patients with myocardial ischemia (6.1% vs 2.8%; P= 0.032) or obstructive CAD without myocardial ischemia (2.9% vs 1.4%; P = 0.004) but not in patients with nonobstructive CAD (1.5% vs 1.4%; P = 0.89) or no CAD (0.3% vs 0.3%; P = 0.68). The CAD phenotype defined by anatomical and functional imaging guides the use of LLM. The presence of myocardial ischemia and anatomical obstructive coronary lesions were associated with a long-term outcome benefit from LLM.

Distinct brain network patterns in complete and incomplete spinal cord injury patients based on graph theory analysis.

To compare the changes in brain network topological properties and structure-function coupling in patients with complete spinal cord injury (CSCI) and incomplete spinal cord injury (ICSCI), to unveil the potential neurobiological mechanisms underlying the different effects of CSCI and ICSCI on brain networks and identify objective neurobiological markers to differentiate between CSCI and ICSCI patients. Thirty-five SCI patients (20 CSCI and 15 ICSCI) and 32 healthy controls (HCs) were included in the study. Here, networks were constructed using resting-state functional magnetic resonance imaging to analyze functional connectivity (FC) and diffusion tensor imaging for structural connectivity (SC). Then, graph theory analysis was used to examine SC and FC networks, as well as to estimate SC-FC coupling values. Compared with HCs, CSCI patients showed increased path length (Lp), decreased global efficiency (Eg), and local efficiency (Eloc) in SC. For FC, ICSCI patients exhibited increased small-worldness, clustering coefficient (Cp), normalized clustering coefficient, and Eloc. Also, ICSCI patients showed increased Cp and Eloc than CSCI patients. Additionally, ICSCI patients had reduced SC-FC coupling values compared to HCs. Moreover, in CSCI patients, the SC network's Lp and Eg values were significantly correlated with motor scores, while in ICSCI patients, the FC network's Cp, Eloc, and SC-FC coupling values were related to sensory/motor scores. These results suggest that CSCI patients are characterized by decreased efficiency in the SC network, while ICSCI patients are distinguished by increased local connections and SC-FC decoupling. Moreover, the differences in network metrics between CSCI and ICSCI patients could serve as objective biological markers, providing a basis for diagnosis and treatment strategies.

Attenuation Tomography Using Low-Frequency Ultrasound for Thorax Imaging: Feasibility Study.

Low-frequency ultrasound can permeate human thorax and can be applied in functional imaging of the respiratory system. In this study, we investigate the transmission of low-frequency ultrasound through the human thorax and propose a waveform matching method to track the changes in the transmission signal during subject's respiration. The method's effectiveness is validated through experiments involving ten human subjects. Furthermore, the experimental findings indicate that the traveltime of the first-arrival signal remains consistent throughout the respiratory cycle. Leveraging this observation, we introduce an algorithm for ultrasound thorax attenuation factor differential imaging. By computing the paths and energy variation of the first-arrival signal from the received waveform, the algorithm reconstructs the distribution of attenuation factor differences between two different thorax states, providing insights into the functional status of the respiratory system. Numerical experiments, using both normal thorax and defective thorax models, confirm the algorithm's feasibility and its robustness against noise, variations in transducer position and orientation. These results highlight the potential of low-frequency ultrasound for bedside, continuous monitoring of human respiratory system through functional imaging.

Feasibility and success of a non-sedated brain MRI training protocol in 7-year-old children from rural and semi-rural Colombia.

Brain magnetic resonance imaging (MRI) is a crucial tool for clinical evaluation of the brain and neuroscience research. Obtaining successful non-sedated MRI in children who live in resource-limited settings may be an additional challenge. To present a feasibility study of a novel, low-cost MRI training protocol used in a clinical research study in a rural/semi-rural region of Colombia and to examine neurodevelopmental factors associated with successful scans. Fifty-seven typically developing Colombian children underwent a training protocol and non-sedated brain MRI at age 7. Group training utilized a customized booklet, an MRI toy set, and a simple mock scanner. Children attended MRI visits in small groups of two to three. Resting-state functional and structural images were acquired on a 1.5-Tesla scanner with a protocol duration of 30-40minutes. MRI success was defined as the completion of all sequences and no more than mild motion artifact. Associations between the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Movement Assessment Battery for Children (MABC), Behavioral Rating Inventory of Executive Function (BRIEF), Child Behavior Checklist (CBCL), and Adaptive Behavior Assessment System (ABAS) scores and MRI success were analyzed. Mean (SD) age at first MRI attempt was 7.2 (0.2) years (median 7.2 years, interquartile range 7.1-7.3 years). Twenty-six (45.6%) participants were male. Fifty-one (89.5%) children were successful across two attempts; 44 (77.2%) were successful on their first attempt. Six (10.5%) were unsuccessful due to refusal or excessive motion. Age, sex, and scores across all neurodevelopmental assessments (MABC, TVIP, ABAS, BRIEF, CBCL, NIH Toolbox Flanker, NIH Toolbox Pattern Comparison, WPPSI) were not associated with likelihood of MRI success (P=0.18, 0.19, 0.38, 0.92, 0.84, 0.80, 1.00, 0.16, 0.75, 0.86, respectively). This cohort of children from a rural/semi-rural region of Colombia demonstrated comparable MRI success rates to other published cohorts after completing a low-cost MRI familiarization training protocol suitable for low-resource settings. Achieving non-sedated MRI success in children in low-resource and international settings is important for the continuing diversification of pediatric research studies.

Optical Assessment of Photoreceptor Function Over the Macula.

The purpose of this study was to develop next-generation functional photoreceptor imaging using ultrahigh-speed swept-source optical coherence tomography (UHS-SS-OCT) and split-spectrum amplitude-decorrelation optoretinography (SSADOR) algorithm. The advancement enables rapid surveying of large retinal areas, promising non-contact, objective, and quantifiable measurements of macular visual function. We designed and built a UHS-SS-OCT prototype instrument using a wavelength tunable laser with 1 MHz A-scan rate. The functional scanning protocol records 5 repeated volumes in 3 seconds. A flash pattern selectively exposes the imaged retina area. SSADOR quantifies photoreceptor light response by extracting optical coherence tomography (OCT) signal changes within the photoreceptor outer segment before and after the flash. The study prospectively enrolled 16 eyes from 8 subjects, demonstrating the ability to measure photoreceptor light response over a record field of view (3 × 3mm2) with high topographical resolution (approximately 100 µm). The measured SSADOR signal corresponds to the flashed pattern, whose amplitude also correlates with flash strength, showing consistency and reproducibility across subjects. The integration of high-performance UHS-SS-OCT and SSADOR enables characterizing photoreceptor function over a clinically meaningful field of view, while maintaining a workflow that can be integrated into routine clinical tests and trials. The new approach allows detecting changes in photoreceptor light response with high sensitivity and can detect small focal impairments. This innovative advance can enable us to detect early photoreceptor abnormalities, as well as help to stage and monitor degenerative retinal diseases, potentially providing a surrogate visual function marker for retinal diseases and accelerating therapeutic development through a safe and efficient outcome endpoint.

Association of Cardiac MRI-derived Aortic Stiffness with Early Stages and Progression of Heart Failure with Preserved Ejection Fraction.

Purpose To investigate if aortic stiffening as detected with cardiac MRI is an early phenomenon in the development and progression of heart failure with preserved ejection fraction (HFpEF). Materials and Methods Both clinical and preclinical studies were performed. The clinical study was a secondary analysis of the prospective HFpEF stress trial (August 2017 through September 2019) and included 48 participants (median age, 69 years [range, 65-73 years]; 33 female, 15 male) with noncardiac dyspnea (NCD, n = 21), overt HFpEF at rest (pulmonary capillary wedge pressure [PCWP] ≥ 15 mm Hg, n = 14), and masked HFpEF at rest diagnosed during exercise stress (PCWP ≥ 25 mm Hg, n = 13) according to right heart catheterization. Additionally, all participants underwent echocardiography and cardiac MRI at rest and during exercise stress. Aortic pulse wave velocity (PWV) was calculated. The mechanistic preclinical study characterized cardiac function and structure in transgenic mice with induced arterial stiffness (Runx2-smTg mice). Statistical analyses comprised nonparametric and parametric comparisons, Spearman correlations, and logistic regression models. Results Participants with HFpEF showed increased PWV (NCD vs masked HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 10.0 m/sec [IQR: 8.0-13.4 m/sec], P = .005; NCD vs overt HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 11.0 m/sec [IQR: 7.5-12.0 m/sec], P = .01). Increased PWV correlated with higher PCWP (P = .006), left atrial and left ventricular long-axis strain (all P < .02), and N-terminal pro-brain natriuretic peptide levels (P < .001). Participants with overt HFpEF had higher levels of myocardial fibrosis, as demonstrated by increased native T1 times (1199 msec [IQR: 1169-1228 msec] vs 1234 msec [IQR: 1208-1255 msec], P = .009). Aortic stiffness was independently associated with HFpEF on multivariable analyses (odds ratio, 1.31; P = .049). Runx2-smTG mice exhibited an "HFpEF" phenotype compared with wild-type controls, with preserved left ventricular fractional shortening but an early and late diastolic mitral annulus velocity less than 1 (mean, 0.67 ± 0.39 [standard error of the mean] vs 1.45 ± 0.47; P = .004), increased myocardial collagen deposition (mean, 11% ± 1 vs 2% ± 1; P < .001), and increased brain natriuretic peptide levels (mean, 171 pg/mL ± 23 vs 101 pg/mL ± 10; P < .001). Conclusion This study provides translational evidence that increased arterial stiffness might be associated with development and progression of HFpEF and may facilitate its early detection. Keywords: MR Functional Imaging, MR Imaging, Animal Studies, Cardiac, Aorta, Heart ClinicalTrials.gov identifier NCT03260621 Supplemental material is available for this article. © RSNA, 2024.

[formula omitted]: A versatile approach for unsupervised segmentation of calcium imaging data

Recent advances in calcium imaging, including the development of fast and sensitive genetically encoded indicators, high-resolution camera chips for wide-field imaging, and resonant scanning mirrors in laser scanning microscopy, have notably improved the temporal and spatial resolution of functional imaging analysis. Nonetheless, the variability of imaging approaches and brain structures challenges the development of versatile and reliable segmentation methods. Standard techniques, such as manual selection of regions of interest or machine learning solutions, often fall short due to either user bias, non-transferability among systems, or computational demand. To overcome these issues, we developed CalciSeg, a data-driven and reproducible approach for unsupervised functional calcium imaging data segmentation. CalciSeg addresses the challenges associated with brain structure variability and user bias by offering a computationally efficient solution for automatic image segmentation based on two parameters: regions’ size limits and number of refinement iterations. We evaluated CalciSeg efficacy on datasets of varied complexity, different insect species (locusts, bees, and cockroaches), and imaging systems (wide-field, confocal, and multiphoton), showing the robustness and generality of our approach. Finally, the user-friendly nature and open-source availability of CalciSeg facilitate the integration of this algorithm into existing analysis pipelines.

Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries in mice

Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific symptoms and risk factors. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following TBIs. Repetitive mild TBIs (rmTBI) compound these issues, resulting in cumulative and long-term brain damage in the brain. In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI by employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI). Our hypothesis is that the effects of rmTBI are worsened in aged animals, with this group showing more pronounced alterations in brain connectivity and white matter structure. Utilizing the closed-head impact model of engineered rotational acceleration (CHIMERA) model, we conducted rmTBIs or sham (control) procedures on young (2.5–3-months-old) and aged (22-months-old) male and female mice to model high-risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposhigh-risking effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean diffusivity, radial diffusivity, axial diffusivity, and fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Neuroinflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in injured aged animals compared to sham aged. These findings offer insight into the interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBI.