ABSTRACT Background and Purpose Solitary tumefactive demyelinating lesions (TDLs) represent an uncommon but clinically significant manifestation of central nervous system demyelination and pose a major diagnostic challenge due to their radiologic resemblance to high‐grade gliomas, primary central nervous system lymphoma, and other mass‐like lesions. Accurate non‐invasive differentiation is essential to avoid unnecessary biopsy and inappropriate oncologic treatment. This review aims to synthesize the role of advanced MRI techniques in improving diagnostic confidence in TDLs. Methods A narrative review of the literature was performed, focusing on advanced MRI modalities used in the evaluation of TDLs, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, and dynamic susceptibility contrast perfusion imaging. Relevant studies were analyzed to identify characteristic imaging patterns and their underlying pathophysiologic correlates. An illustrative case was incorporated to contextualize these findings. Results Advanced MRI techniques demonstrate distinct imaging signatures in TDLs that reflect inflammatory demyelination rather than neoplastic processes. Proton MR spectroscopy typically reveals elevated choline with preserved or relatively less reduced N‐acetylaspartate and the presence of lipid–lactate peaks. Diffusion imaging shows variable restriction corresponding to active inflammatory fronts. Magnetization transfer imaging highlights myelin disruption, often with characteristic peripheral signal changes. Perfusion imaging consistently demonstrates low relative cerebral blood volume, reflecting the absence of neoangiogenesis, in contrast to high‐grade tumors. Integration of these modalities improves diagnostic specificity and reduces reliance on invasive procedures. Conclusions Advanced multimodal MRI provides critical complementary information for differentiating TDLs from neoplastic mimics. A combined imaging approach, supported by pathophysiologic understanding, can enhance diagnostic accuracy and guide appropriate clinical management. Incorporation of illustrative cases further strengthens the practical application of these techniques in routine clinical practice.

Study design:(Phantom & Human)Objective:The purpose of this study was to optimize imaging sequences to suppress artifacts induced by metallic hardware, using phantoms implanted with spinal hardware and participants with spinal cord injury (SCI) and spinal hardware at 3Tesla.Settings:USMethods:Magnetic resonance (MR) sequences were first tested on realistic agar-suspended spine phantom models with metallic instrumentation. C-spine with anterior-plate, posterior rods/screws, C-spine with rods/screws, C-spine with Kirschner wire, posterior T-spine with rods/screws, and anterior/posterior T-spine with anterior-plate and rods/screws were used. The optimized metal-suppression sequences obtained from phantom imaging were then evaluated on sixteen participants with SCI with similar metal implants. Four neuroradiologists performed a qualitative analysis and ranked all the scans, both with and without metal suppression. The following subjective visual assessment included: conspicuity of neural foramen, mitigation of artifact, visualization of the spinal cord and homogeneity of the cerebrospinal fluid (CSF).Results:Agreement between the raters was moderate (0.41 to 0.6) to substantial (0.61 to 0.8) for most measures, although some were in the fair range (0.21 to 0.4). In evaluating the T2 weighted-axial images for conspicuity of neural foramen, visualization of spinal cord, and homogeneity of CSF as well as T1 weighted-axial image for homogeneity of CSF in the anterior plate, the upper bound of the confidence interval was below "3" so the metal suppressed image was favored.Conclusion:There is some improvement in using metal-suppressed sequences to evaluate spinal cord injury patients with metal hardware at 3T MRI; however, the model-adjusted mean scores did not reach statistical significance.

PURPOSE:This multi-institutional study investigates how preoperative functional MRI (fMRI) and diffusion tensor imaging (DTI) influence surgical decision-making and clinical outcomes in patients undergoing brain tumor resection. METHODS AND MATERIALS:Seventy patients from four academic centers: Thomas Jefferson University (TJU), n=51, University Hospital Basel, n=11; University of Pennsylvania (UPenn), n=4, and Johns Hopkins University (JHU) n=3, underwent preoperative task-based fMRI and DTI. Six neurosurgeons completed structured pre- and post-imaging surveys evaluating changes in surgical approach, craniotomy planning, extent of resection, operative duration, and diagnostic confidence. RESULTS:Integration of fMRI and DTI into surgical planning resulted in a significant shift from awake to asleep craniotomies, especially at TJU (P = 0.01), with "asleep craniotomy" increasing to 51% overall (Chi-square P < .0001). fMRI led to a "much more aggressive" surgical plan in 39% of cases globally, most prominently at TJU (74%) and UPenn (50%), while JHU reported a decrease in aggressiveness in 33.3% of cases. DTI had a similar but slightly reduced impact, with "much more aggressive" being the top response (34%). fMRI was rated as more clinically valuable than DTI in 53.4% of cases overall with TJU having the highest rate (72%). Postoperatively, a larger extent of resection was reported in 61% of cases, with shorter-than-expected surgical durations in 51%. Overall, combined fMRI/DTI had a significant "strong positive" influence on surgery in 71% and clinical care in 68% of cases, with significant inter-institutional differences (P < 0.001). CONCLUSION:Preoperative fMRI and DTI significantly reshape neurosurgical planning by optimizing resection strategies. Most notably, preoperative mapping facilitated a significant shift from awake to asleep craniotomies, contributing to shorter than expected surgical durations without compromising the extent of resection.

BACKGROUND AND PURPOSE:Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a promising noninvasive method for evaluating water motion that may reflect glymphatic system function. However, the reliability of DTI-ALPS measurements across different region-of-interest (ROI) selection methods remains underinvestigated. This study aimed to assess the interrater reliability among three neuroradiologists in native space and compare DTI-ALPS indices derived from ROIs placed in subjects' native space versus standardized Montreal Neurological Institute (MNI) space. METHODS:DTI-ALPS indices from 16 healthy subjects were calculated from both left and right hemispheres using two ROI placement approaches: (1) native space ROIs manually placed by three neuroradiologists, and (2) standardized ROIs in MNI space based on the fractional anisotropy template. Interrater reliability was assessed using intraclass correlation coefficients (ICCs). The proportion of ROI overlaps among the three neuroradiologists was also evaluated. Differences between native and MNI space measurements were evaluated using related-samples Friedman's analysis with post hoc pairwise comparisons. RESULTS:Interrater reliability for native space ROI placement was moderate for left-sided DTI-ALPS indices (ICC = 0.599) and good for right-sided DTI-ALPS indices (ICC = 0.807). Spatial overlap analysis revealed poor Dice similarity coefficients across all ROI types (range: 0.047-0.312), with right association ROIs showing higher spatial consistency. Significant differences were found between native and MNI space measurements for left-sided DTI-ALPS indices (p = 0.002) but not for right-sided DTI-ALPS indices (p = 0.913). CONCLUSION:These findings highlight the importance of standardized ROI selection approaches for clinical applications of DTI-ALPS.

BACKGROUND AND OBJECTIVE:Venous manometry (VM) is the reference standard for confirming hemodynamically significant transverse sinus stenosis (TSS) in idiopathic intracranial hypertension (IIH). However, no standardized approach exists for triaging refractory IIH (rIIH) patients for VM, and current IIH diagnostic criteria were not designed for this purpose. We evaluated the performance of established IIH diagnostic frameworks and imaging markers in detecting VM-confirmed TSS (vTSS). METHODS:We retrospectively reviewed consecutive rIIH patients undergoing VM at a tertiary center (2022-2023). vTSS was defined as a trans-stenotic pressure gradient ≥8 mm Hg. Four IIH frameworks (Friedman 2013, modified Dandy 2014, Korsbæk 2023, and a modified 2023 schema), and predefined vascular and non-vascular MRI/MR venography signs were compared against vTSS. RESULTS:Among 48 rIIH patients (mean age 38.9±9.9 years; all female; body mass index 36.8±9.1 kg/m²), vTSS was present in 33/48 (68.8%). Sensitivity/specificity for vTSS were: Friedman 2013 (78.6%/53.8%), modified Dandy 2014 (83.3%/60.0%), Korsbaek 2023 (90.6%/35.7%), and modified 2023 (93.5%/35.7%). Vascular imaging signs were highly sensitive (96.3%) across definitions; the modified 2023 vascular criteria achieved the highest specificity (42.9%). Five (15.2%) vTSS patients lacked papilledema. CONCLUSION:Current IIH frameworks vary in accuracy for detecting vTSS. 2023-based criteria maximize sensitivity for vTSS, while modified Dandy 2014 criteria offer greater specificity. Vascular imaging signs outperform non-vascular signs. These findings support incorporating standardized imaging protocols and refined triage algorithms to optimize VM referral in rIIH.

Idiopathic Intracranial hypertension (IIH), also referred to as pseudotumor cerebri, is a term used to describe increased intracranial pressure in the absence of a known identifiable secondary cause. Despite advancements of neuroimaging techniques, imaging of the pathological underpinnings in the diagnosis of IIH has been limited. Although the causation of IIH has been ascribed to increased Cerebrospinal Fluid production and disordered drainage through the dural sinuses, new evidence shows that the glymphatic system which is an alternate pathway of drainage is likely to play a pivotal role. In this review, we address the pathophysiological underpinnings in the causation of IIH and discusses characteristic anatomical imaging findings on conventional MRI and explore the role of advanced imaging techniques.

Purpose/Hypothesis: Early detection of respiratory impairments in amyotrophic lateral sclerosis (ALS) has profound implications for survival and quality of life. Identifying these impairments can enhance disease monitoring and support targeted disease ameliorating therapies. However, early detection of respiratory impairments is hindered by clinical tests that inadequately challenge the respiratory neural drive. Unlike limb muscles, respiratory muscles are innervated by two independent but overlapping neural pathways: the ponto-medullary-spinal pathway for involuntary/automatic breathing and the cortico-spinal pathway for volitional breathing. ALS respiratory care guidelines focus on volitional breathing tests like functional vital capacity (FVC) and maximum inspiratory pressure (MIP), which may miss early impairments in automatic breathing. The purpose of this study is to detect if subclinical impairments in automatic breathing are present, despite normal volitional respiratory measures such as FVC and MIP, in the asymptomatic phase of ALS. To confirm the histopathological correlates of early breathing impairments in ALS, we also performed MRI diffusion tensor imaging (DTI) of the cervical spinal cord and neurofilament level estimation in the blood. Materials and Methods: This observational study included asymptomatic ALS ( C9orf72 gene carriers, C9; n=6; aged 46.5±9.3 years, female=4), healthy controls (n=6; aged 39.5±7.9 years, female=3), and symptomatic ALS of heterogeneous etiology (n=3; aged 57.33±14.05 years, female=2). Tests measured 1) maximum volitional respiratory force (MIP and sniff nasal inspiratory pressure, SNIP) and volume production (FVC); 2) automatic respiratory drive (mouth occlusion pressure, P0.1, and waking average oxygen saturation [~30 min epoch of waking SpO 2 %]). Histopathology in asymptomatic C9 carriers was confirmed using diffusion MR (iFOV-HYDI) imaging to assess changes in the cervical spinal cord (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) compared to healthy controls with an unpaired T-test. Blood samples are currently being processed for neurofilament analysis. Results: Symptomatic ALS participants showed significant reductions in volitional respiratory measures: MIP=-52±32 cm H 2 O, SNIP=-35±21 cm H 2 O, and FVC=1.95±0.95 L/s ( p<0.05 ). No deficits in volitional respiratory measures were observed in C9 carriers: MIP=-125±17 cm H 2 O, SNIP=-104±16 cm H 2 O, and FVC=3.5±0.91 L/s. However, C9 carriers aged >48 years showed significant deficits in automatic respiratory measures: P0.1=1.14±0.43 cm H 2 O and SpO 2 =92.4±2.14%. DTI FA analysis showed lower values in asymptomatic C9 carriers, with significant differences compared to healthy controls at the C6 cord ( p<0.05 ), indicating loss of white matter integrity; higher radial diffusivity (RD) indicating greater myelin sheath disruption; and lower axial diffusivity (AD) indicating white matter axonal damage at the C4 spinal cord ( p<0.05 ), the core region for the phrenic motor pool. Conclusions: This study highlights the utility of automatic breathing measures in detecting early ALS progression in asymptomatic individuals. Preliminary results suggest reduced automatic brainstem respiratory neural drive in C9 carriers without concomittant deficits in conventional volitional breathing measures. Histopathological evidence of early impairments in C9 carriers was also evident with MRI DTI analysis. This multimodal biomarker approach could fill a critical gap in ALS care by providing markers for earlier intervention and endpoints in future clinical trials. Thomas Jefferson University Provost Award 2022-23 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Facilitating placental transfusion—the transfer of blood from the placenta to the newborn—via delayed cord clamping (DCC) or umbilical cord milking (UCM) at birth has been shown to improve iron stores in healthy term infants and may positively impact long-term neurodevelopmental outcomes. Infants who are non-vigorous at birth and at risk of developing hypoxic-ischemic encephalopathy (HIE) are particularly likely to benefit from placental transfusion. This process may offer neuroprotection by enhancing cardiopulmonary transition, supporting cardiac preload, improving systemic and cerebral perfusion, delivering stem cells and neurotrophic factors, and preventing iron deficiency. While DCC is not currently recommended for non-vigorous term infants requiring immediate resuscitation, UCM offers a viable alternative, as it can be performed quickly. This study is a multicenter, cluster-randomized, crossover-controlled trial comparing UCM with early cord clamping (ECC) in term and late preterm infants who are non-vigorous at birth. The trial will be conducted across seven centers in India. Before the trial begins, each site will be assigned to an initial study arm using a computer-generated randomization scheme. Once 50

INTRODUCTION: Glioma-induced brain network reorganization often leads to neurological deficits, which vary depending on tumor location. METHODS: Resting-state fMRI was conducted on 32 patients, including 15 with left temporal lesions and 17 with left frontal glioma. Group independent component analysis (ICA) was employed to extract networks, excluding tumor-affected areas, followed by dFC analysis using the sliding window method and k-means clustering. A two-sample t-test compared dFC between speech-deficit and normal speech patients in each group. (p < 0.05) RESULTS: Four recurring FC "States" for temporal tumors and five for frontal tumors extracted. Statistically significant dFC differences were observed between language deficit and normal language groups in states 2–4 for temporal tumors and states 2-5 for frontal tumors. In left temporal tumor patients, speech deficit correlated with increased FC between Visual Network (VN) and Salience/Sensory-motor networks in state 3, and reduced FC between Salience and the right frontoparietal network in state 4. Similarly, in left frontal tumor patients with language deficits, increased FC within the visual network and between visual and salience networks in states 2 and 3 were noted, along with decreased FC between the language network and dorsal attention/frontoparietal networks in state 5. CONCLUSIONS: Overall, our findings highlightes how brain glioma affects dFC within and between resting-state networks, particularly concerning language deficits, suggesting network reorganization and offering insights into tumor-related neurological disruptions' pathophysiology, which could potentially enhance treatment strategies and outcomes for patients.

BACKGROUND AND PURPOSE:Neuropathic pain (NP) is a debilitating condition following spinal cord injury (SCI). The role of periaqueductal gray (PAG) in NP development following SCI remains underexplored. Using resting-state functional MRI (rsfMRI), our study aimed to demonstrate the alterations in functional connectivity (FC) of PAG in NP following SCI. METHODS:Ten SCI patients (SCI + NP, n = 7, and SCI - NP, n = 3), alongside 10 healthy controls (HCs), were enrolled. rsfMRI was conducted followed by seed-to-voxel analysis using PAG as the seed region and then group-based analysis comprising three groups (SCI + NP, SCI - NP, and HC). Age and gender were considered as confounding variables. RESULTS:Compared to HCs, SCI + NP demonstrated decreased FC between PAG and right insula, right frontal orbital cortex, right pallidum, dorsal raphe nucleus (DRN), red nuclei (RN), substantia nigra (SN), and ventral posterolateral (VPL) thalamic nuclei. Compared to SCI - NP, SCI + NP demonstrated increased FC between PAG and posterior cingulate cortex (PCC), hippocampus, cerebellar vermis lobules IV and V, and thalamic structures (posterior and lateral pulvinar, the mediodorsal nuclei, and the ventral lateral nuclei). Additionally, decreased FC between the PAG and VPL, geniculate bodies, intralaminar nuclei of thalamus, DRN, RN, SN, and prefrontal cortex was observed in this comparison. CONCLUSIONS:Altered FC between PAG and right anterior insula, VPL, DRN, RN, SN, cerebellar vermis lobules IV and V, frontal cortex, and PCC was associated with NP sequelae of SCI. Additionally, SCI was independently associated with decreased FC between PAG and right posterior insula, cerebellar lobules IV and V, and cerebellar vermis lobules III, IV, and V.

ObjectiveSpinal cord stimulation (SCS) is an invasive treatment option for patients suffering from chronic low-back pain (cLBP). It is an effective treatment that has been shown to reduce pain and increase the quality of life in patients. However, the activation of pain processing regions of cLBP patients receiving SCS has not been assessed using objective, quantitative functional imaging techniques. The purpose of the present study was to compare quantitative resting-state (rs)-fMRI and arterial spin labeling (ASL) measures between SCS patients and healthy controls and to correlate clinical measures with quantitative multimodal imaging indices in pain regions.MethodsMulti-delay 3D GRASE pseudo-continuous ASL and rs-fMRI data were acquired from five patients post-SCS with cLBP and five healthy controls. Three ASL measures and four rs-fMRI measures were derived and normalized into MNI space and smoothed. Averaged values for each measure from a pain atlas were extracted and compared between patients and controls. Clinical pain scores assessing intensity, sensitization, and catastrophizing, as well as others assessing global pain effects (sleep quality, disability, anxiety, and depression), were obtained in patients and correlated with pain regions using linear regression analysis.ResultsArterial transit time derived from ASL and several rs-fMRI measures were significantly different in patients in regions involved with sensation (primary somatosensory cortex and ventral posterolateral thalamus [VPL]), pain input (posterior short gyrus of the insula [PS]), cognition (dorsolateral prefrontal cortex [DLPC] and posterior cingulate cortex [PCC]), and fear/stress response (hippocampus and hypothalamus). Unidimensional pain rating and sensitization scores were linearly associated with PS, VPL, DLPC, PCC, and/or amygdala activity in cLBP patients.ConclusionThe present results provide evidence that ASL and rs-fMRI can contrast functional activation in pain regions of cLBP patients receiving SCS and healthy subjects, and they can be associated with clinical pain evaluations as quantitative assessment tools.

Objective This study aimed to analyze the association between acute kidney injury (AKI) and abnormalities on brain magnetic resonance imaging (MRI) or death in neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE).Study Design This is a retrospective case-control analysis of 380 neonates born at & GE;35 weeks' gestation treated with therapeutic hypothermia for HIE. Death or abnormal brain MRI using the basal ganglia watershed scoring system was compared between neonates with and without AKI.Results A total of 51 (13.4%) neonates had AKI. Infants with AKI had higher rates of the composite of death or abnormal brain MRI (74.5 vs. 38.3%; p < 0.001). Rate of death (21.6 vs. 5.5%; p < 0.001) and severe abnormalities on MRI or death (43.1 vs. 19.1%; p < 0.001) were also higher in neonates with AKI.Conclusion AKI is strongly associated with abnormalities on brain MRI or death in neonates with HIE. Identification of AKI in this patient population may be helpful in guiding clinical management and predicting potential neurodevelopmental impairment.

This review surveys concussion management, focusing on the use of neuroimaging techniques in return to play (RTP) decisions. Clinical assessments traditionally were the foundation of concussion diagnoses. However, their subjective nature prompted an exploration of neuroimaging modalities to enhance diagnosis and management. Magnetic resonance spectroscopy provides information about metabolic changes and alterations in the absence of structural abnormalities. Diffusion tensor imaging uncovers microstructural changes in white matter. Functional magnetic resonance imaging assesses neuronal activity to reveal changes in cognitive and sensorimotor functions. Positron emission tomography can assess metabolic disturbances using radiotracers, offering insight into the long-term effects of concussions. Vestibulo-ocular dysfunction screening and eye tracking assess vestibular and oculomotor function. Although these neuroimaging techniques demonstrate promise, continued research and standardization are needed before they can be integrated into the clinical setting. This review emphasizes the potential for neuroimaging in enhancing the accuracy of concussion diagnosis and guiding RTP decisions.

INTRODUCTION: Multi-delay, pseudo-continuous arterial spin labelling (PCASL) is a novel technique capable of perfusion imaging without contrast. It overcomes the limitation of a low signal-to-noise ratio of pulsed-ASL, and multiple post-label delays allow it to account for and measure arterial transit time (ATT). This makes it a suitable tool for the perfusion assessment. To date, there have been no studies to assess changes in ASL-measured perfusion in chronic low-back pain (cLBP) patients treated with thoracic spinal cord stimulation (tSCS). METHODS: PCASL data was acquired in five patients post-tSCS and five healthy subjects. ATT was estimated using weighted delays from multiple delay times, and it was used to calculate cerebral blood flow (CBF) and cerebral blood volume (CBV). Maps were normalized into MNI space and smoothed. Averaged values of ATT, CBF and CBV from pain ROI atlas were extracted and compared between cLBP and healthy control groups. Statistics comparing perfusion changes between patients and healthy subjects were conducted after Box-Cox transformation of data using Wilcoxon rank sum. RESULTS: Our results demonstrated the feasibility of MRI scanning with ASL sequence in patients with SCS. Specific absorption rates ranged from 0.031–0.042W/kg. Wilcoxon test indicated that ATT was significantly greater in cLBP patients within the supplementary motor area, posterior short gyrus, and the orbitofrontal cortex. There were no significant differences in patients and controls in CBF or CBV. CONCLUSIONS: Rate of perfusion as indexed by PCASL-derived ATT is reduced in cLBP treated with SCS patients in regions associated with pain processing, cognition, and motor planning. Insignificant results in CBF and CBV measures are likely due to low sample size of patients.

To determine the incidence of acute neuroimaging (NI) findings and comorbidities in the coronavirus disease of 2019 (COVID‐19)‐infected subjects in seven U.S. and four European hospitals.