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Background: The choroid plexus (ChP), a densely vascularized structure, has drawn increasing attention for its involvement in brain homeostasis and waste clearance. While the volumetric changes have been explored in many imaging studies, few studies have investigated the vascular degeneration associated with aging in the ChP., Purpose: To investigate the sub-structural characteristics of the ChP, particularly the vascular compartment using high-resolution 7T imaging enhanced with Ferumoxytol, an ultrasmall super-paramagnetic iron oxide, which greatly increase the susceptibility contrast for vessels., Study Type: Prospective., Subjects: Forty-nine subjects without neurological disorders (age: 21-80 years; 42 ± 17 years; 20 females)., Field Strength/sequence: 7-T with 2D and 3D T2* GRE, 3D MPRAGE T1, 2D TSE T2, and 2D FLAIR., Assessment: The vascular and stromal compartments of the ChP were segmented using K-means clustering on post-contrast 2D GRE images. Visual and qualitative assessment of ChP vascular characteristics were conducted independently by three observers. Vascular density (Vol vessel /Vol ChP ratio) and susceptibility change (Δχ) induced by Ferumoxytol were analyzed on 3D GRE-derived susceptibility-weighted imaging and quantitative susceptibility mapping, respectively., Statistical Tests: Independent t-test, Mann-Whitney U test, and Chi-square test were utilized for group comparisons. The relationship between age and ChP's vascular alterations was examined using Pearson's correlation. Intra-class coefficient was calculated for inter-observer agreement. A P value <0.05 was considered statistically significant., Results: 2D GRE images demonstrated superior contrast and accurate delineation of ChP substructures (ICC = 0.86). Older subjects exhibited a significantly smaller vascular density (16.5 ± 4.34%) and lower Δχ (22.10 ± 12.82 ppb) compared to younger subjects (24.85 ± 6.84% and 34.64 ± 12.69 ppb). Vascular density and mean Δχ within the ChP negatively correlated with age (r = -0.48, and r = -0.45)., Data Conclusion: Ferumoxytol-enhanced 7T images can demonstrate ChP alterations in elderly with decreased vascular density and expansion of nonvascular compartment., Evidence Level: 1 TECHNICAL EFFICACY: Stage 2., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

The intricate neurofluid dynamics and balance is essential in preserving the structural and functional integrity of the brain. Key among these forces are: hemodynamics, such as heartbeat-driven arterial and venous blood flow, and hydrodynamics, such as cerebrospinal fluid (CSF) circulation. The delicate interplay between these dynamics is crucial for maintaining optimal homeostasis within the brain. Currently, the widely accepted framework for understanding brain functions is the Monro-Kellie's doctrine, which posits a constant sum of intracranial CSF, blood flow and brain tissue volumes. However, in recent decades, there has been a growing interest in exploring the dynamic interplay between these elements and the impact of external factors, such as daily changes in body position. CSF circulation in particular plays a crucial role in the context of neurodegeneration and dementia, since its dysfunction has been associated with impaired clearance mechanisms and accumulation of toxic substances. Despite the implementation of various invasive and non-invasive imaging techniques to investigate the intracranial hemodynamic or hydrodynamic properties, a comprehensive understanding of how all these elements interact and are influenced by body position remains wanted. Establishing a comprehensive overview of this topic is therefore crucial and could pave the way for alternative care approaches. In this review, we aim to summarize the existing understanding of intracranial hemodynamic and hydrodynamic properties, fundamental for brain homeostasis, along with factors known to influence their equilibrium. Special attention will be devoted to elucidating the effects of body position shifts, given their significance and remaining ambiguities. Furthermore, we will explore recent advancements in imaging techniques utilized for real time and non-invasive measurements of dynamic body fluid properties in-vivo ., Competing Interests: DC, LM, and LB were employed by FONAR Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Muccio, Sun, Chu, Damadian, Minkoff, Bonanni and Ge.)

Objectives: To determine the association of adequate empirical combination therapy (AECT) with 30-day all-cause mortality in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections (BSI)., Methods: This multicentre, retrospective cohort study analysed data from 14 public hospitals in Italy, including all consecutive adult patients admitted during 2021-2022 with septic shock due to P. aeruginosa BSI. We compared the outcomes of patients receiving AECT to those on adequate empirical monotherapy (AEMT) using Cox regression analyses., Results: Of the 98 patients who received adequate empirical antibiotic treatment for septic shock due to P. aeruginosa BSI, 24 underwent AECT and 74 were given AEMT. AECT was associated with a lower 30-day all-cause mortality (25%, six out of 24) compared to AEMT (56.8%, 42 out of 74; P = 0.007). Multivariate Cox regression analysis indicated AECT as the only factor significantly associated with improved survival (aHR 0.30; 95% CI 0.12-0.71; P = 0.006). By contrast, the use of monotherapy or combination therapy in the definitive regimen did not influence mortality (aHR 0.73; 95% CI 0.25-2.14; P = 0.568)., Conclusions: AECT may be associated with reduced mortality compared to monotherapy in septic shock patients due to P. aeruginosa BSI. However, the administration of definitive adequate monotherapy or combination therapy yields similar outcomes, suggesting that once susceptibility is documented, switching to a single active in vitro drug is safe and feasible. Further studies are recommended to validate these findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique with simultaneous (during stimulation) and cumulative effects (after repeated sessions) on blood flow and neuronal metabolism. These effects remain mostly unclear especially in multiple sclerosis (MS). This work aims to elucidate brain metabolic and hemodynamic underpinnings of tDCS and its potential therapeutic impact in MS patients using quantitative tDCS-MRI., Methods: MS participants (n = 20; age = 45.4 ± 12.3 years, 7 males) underwent 3 T MRI scans before and after 20 daily sessions of dorsolateral prefrontal cortex (DLFPC) tDCS (2.0 mA, left anodal) paired with adaptive cognitive training (aCT). During both visits, imaging measurements of cerebral blood flow (CBF), cerebral venous blood oxygenation (Yv) and calculated cerebral metabolic rate of oxygen (CMRO 2 ) were obtained at pre-tDCS, during-tDCS and post-tDCS., Results: At baseline, significant increase from pre- to during-tDCS was observed in CMRO 2 (7.6%; p  = 0.002), CBF (11.0%; p  < 0.0001) and Yv (1.9%; p  = 0.006). At follow up, we observed an increase in pre-tDCS CMRO 2 (140.59 ± 13.83 μmol/100 g/min) compared to baseline pre-tDCS levels (128.30 ± 14.00 μmol/100 g/min; p  = 0.006). Sustained elevations in CMRO 2 and CBF into post-tDCS were also observed (tDCS lingering effects). Cumulative tDCS effects were observed in the form of sustained elevations in CMRO 2 and CBF in pre-tDCS follow up, reaching the magnitudes measured at baseline during-tDCS., Discussion: TDCS induces an acute surge in metabolic activity persisting immediately after the stimulation is removed. Moreover, treatment composed of repeated tDCS-aCT paired sessions contributes to establishing long-lasting increases in neuronal activity., Competing Interests: Soterix Medical Inc. provided the tDCS equipment used for research use. The City University of New York holds patents on brain stimulation with MB as inventor. The City University of New York holds patents on brain stimulation with AD as inventor. AD is an employee of Soterix Medical Inc. AD has equity in Soterix Medical Inc. MB has equity in Soterix Medical Inc. MB consults, received grants, assigned inventions, and/or serves on the SAB of SafeToddles, Boston Scientific, GlaxoSmithKline, Biovisics, Mecta, Lumenis, Halo Neuroscience, Google-X, i-Lumen, Humm, Allergan (Abbvie), Apple. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Muccio, Pilloni, Walton Masters, He, Krupp, Datta, Bikson, Charvet and Ge.)

Mapping the small venous vasculature of the hippocampus in vivo is crucial for understanding how functional changes of hippocampus evolve with age. Oxygen utilization in the hippocampus could serve as a sensitive biomarker for early degenerative changes, surpassing hippocampal tissue atrophy as the main source of information regarding tissue degeneration. Using an ultrahigh field (7T) susceptibility-weighted imaging (SWI) sequence, it is possible to capture oxygen-level dependent contrast of submillimeter-sized vessels. Moreover, the quantitative susceptibility mapping (QSM) results derived from SWI data allow for the simultaneous estimation of venous oxygenation levels, thereby enhancing the understanding of hippocampal function. In this study, we proposed two potential imaging markers in a cohort of 19 healthy volunteers aged between 20 and 74 years. These markers were: 1) hippocampal venous density on SWI images and 2) venous susceptibility (Δχ vein ) in the hippocampus-associated draining veins (the inferior ventricular veins (IVV) and the basal veins of Rosenthal (BVR) using QSM images). They were chosen specifically to help characterize the oxygen utilization of the human hippocampus and medial temporal lobe (MTL). As part of the analysis, we demonstrated the feasibility of measuring hippocampal venous density and Δχ vein in the IVV and BVR at 7T with high spatial resolution (0.25 × 0.25 × 1 mm 3 ). Our results demonstrated the in vivo reconstruction of the hippocampal venous system, providing initial evidence regarding the presence of the venous arch structure within the hippocampus. Furthermore, we evaluated the age effect of the two quantitative estimates and observed a significant increase in Δχ vein for the IVV with age (p=0.006, r 2 = 0.369). This may suggest the potential application of Δχ vein in IVV as a marker for assessing changes in atrophy-related hippocampal oxygen utilization in normal aging and neurodegenerative diseases such as AD and dementia., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to develop and test a 3D multi-parameter MR fingerprinting (MRF) method for brain imaging applications. The subject cohort included 5 healthy volunteers, repeatability tests done on 2 healthy volunteers and tested on two multiple sclerosis (MS) patients. A 3D-MRF imaging technique capable of quantifying T 1 , T 2 and T 1ρ was used. The imaging sequence was tested in standardized phantoms and 3D-MRF brain imaging with multiple shots (1, 2 and 4) in healthy human volunteers and MS patients. Quantitative parametric maps for T 1 , T 2 , T 1ρ , were generated. Mean gray matter (GM) and white matter (WM) ROIs were compared for each mapping technique, Bland-Altman plots and intra-class correlation coefficient (ICC) were used to assess repeatability and Student T-tests were used to compare results in MS patients. Standardized phantom studies demonstrated excellent agreement with reference T 1 /T 2/ T 1ρ mapping techniques. This study demonstrates that the 3D-MRF technique is able to simultaneously quantify T 1 , T 2 and T 1ρ for tissue property characterization in a clinically feasible scan time. This multi-parametric approach offers increased potential to detect and differentiate brain lesions and to better test imaging biomarker hypotheses for several neurological diseases, including MS.

Aim: This perspective paper illustrates the usefulness of explicitly integrating motor learning terminology with evolving therapeutic approaches. Physiotherapy specific scoliosis exercises (PSSEs) include a growing number of approaches to scoliosis management and serve as an example of this integration., Methods: Three quintessential patient cases (a young hypermobile adolescent, a post-pubescent teen, and an adult with childhood diagnosis of scoliosis) serve to contrast the clinical decision-making process for a PSSE plan of care when organized within a motor learning framework., Conclusions and Implications: As intervention approaches evolve, aligning the unique terminologies from different schools of thought with motor learning constructs would provide a common language for clinicians, academics and researchers to facilitate comparison of approaches and organize intervention care plans. Linking a motor learning framework and terminology to PSSE may facilitate comparison of PSSE treatment approaches by clinicians, academics, and researchers, as well as advance the global quality of care for patients with scoliosis.

Background: Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive technique used for cortical excitability modulation. tDCS has been extensively investigated for its clinical applications; however further understanding of its underlying in-vivo physiological mechanisms remains a fundamental focus of current research., Objectives: We investigated the simultaneous effects of tDCS on cerebral blood flow (CBF), venous blood oxygenation (Yv) and cerebral metabolic rate of oxygen (CMRO 2 ) using simultaneous MRI in healthy adults to provide a reference frame for its neurobiological mechanisms., Methods: Twenty-three healthy participants (age = 35.6 ± 15.0 years old, 10 males) completed a simultaneous tDCS-MRI session in a 3 T scanner fitted with a 64-channels head coil. A MR-compatible tDCS device was used to acquire CBF, Yv and CMRO 2 at three time points: pre-, during- and post- 15 minutes of 2.0 mA tDCS on left anodal dorsolateral prefrontal cortex., Results: During tDCS, CBF significantly increased (57.10 ± 8.33 mL/100g/min) from baseline (53.67 ± 7.75 mL/100g/min; p < 0.0001) and remained elevated in post-tDCS (56.79 ± 8.70 mL/100g/min). Venous blood oxygenation levels measured in pre-tDCS (60.71 ± 4.12 %) did not significantly change across the three timepoints. The resulting CMRO 2 significantly increased by 5.9 % during-tDCS (175.68 ± 30.78 µmol/100g/min) compared to pre-tDCS (165.84 ± 25.32 µmol/100g/min; p = 0.0015), maintaining increased levels in post-tDCS (176.86 ± 28.58 µmol/100g/min)., Conclusions: tDCS has immediate effects on neuronal excitability, as measured by increased cerebral blood supply and oxygen consumption supporting increased neuronal firing. These findings provide a standard range of CBF and CMRO 2 changes due to tDCS in healthy adults that may be incorporated in clinical studies to evaluate its therapeutic potential., Competing Interests: Declaration of Competing Interest Soterix Medical Inc. provided the tDCS equipment used for research use. The City University of New York holds patents on brain stimulation with MB as inventor. The City University of New York holds patents on brain stimulation with AD as inventor. AD is an employee of Soterix Medical Inc. AD has equity in Soterix Medical Inc. MB has equity in Soterix Medical Inc. MB consults, received grants, assigned inventions, and/or serves on the SAB of SafeToddles, Boston Scientific, GlaxoSmithKline, Biovisics, Mecta, Lumenis, Halo Neuroscience, Google-X, i-Lumen, Humm, Allergan (Abbvie), Apple., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The vascular tortuosity (VT) of the internal carotid artery (ICA), and vertebral artery (VA) can impact blood flow and neuronal function. However, few studies involved quantitative investigation of VT based on magnetic resonance imaging (MRI). The main purpose of our study was to evaluate the age and gender effects on ICA and VA regarding the tortuosity and flow changes by applying automatic vessel segmentation, centerline tracking, and phase mapping on MR angiography., Methods: A total of 247 subjects (86 males and 161 females) without neurological diseases participated in this study. All subjects obtained T1-weighted MRI, 3D time-of-flight MR angiography, and 2D phase-contrast (PC) MRI scans. To generate quantitative tortuosity metrics from TOF images, the vessel segmentation and centerline tracking were implemented based on Otsu thresholding and fast marching algorithms, respectively. Blood flow and velocity were measured using PC MRI. Among the 247 subjects, 144 subjects (≤ 60 years, 49 males/95 females) were categorized as the young group; 103 subjects (>60 years, 37 males/66 females) were categorized as the old group., Results: Independent t -test showed that older subjects had higher tortuosity metrics, whereas lower blood flow and velocity than young subjects ( p < 0.0025, Bonferroni-corrected). Cerebral blood flow calculated using the sum flux of four target arteries normalized by the brain mass also showed significantly lower values in older subjects ( p < 0.001). The age was observed to be positively correlated with the VT metrics. Compared to the males, the females demonstrated higher geometric indices within VAs as well as faster age-related vascular profile changes. After adjusting age and gender as covariates, maximum blood velocity is negatively correlated with geometric measurements. No association was observed between blood flux and geometric measures., Conclusions: Vascular auto-segmentation, centerline tracking, and phase mapping provide promising quantitative assessments of tortuosity and its effects on blood flow. The neck arteries demonstrate quantifiable and significant age-related morphological and hemodynamic alterations. Moreover, females showed more distinct vascular changes with age. Our work is built upon a comprehensive quantitative investigation of a large cohort of populations covering adult lifespan using MRI, the results can serve as reference ranges of each decade in the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Jiang, Liu, Muccio, Li, Cao, Wisniewski, Lu and Ge.)

Background: Cerebrospinal fluid (CSF) circulation between the brain and spinal canal, as part of the glymphatic system, provides homeostatic support to brain functions and waste clearance. Recently, it has been observed that CSF flow is strongly driven by cardiovascular brain pulsation, and affected by body orientation. The advancement of MRI has allowed for non-invasive examination of the CSF hydrodynamic properties. However, very few studies have addressed their relationship with body position (e.g., upright versus supine). It is important to understand how CSF hydrodynamics are altered by body position change in a single cardiac phase and how cumulative long hours staying in either upright or supine position can affect craniocervical CSF flow., Methods: In this study, we investigate the changes in CSF flow at the craniocervical region with flow-sensitive MRI when subjects are moved from upright to supine position. 30 healthy volunteers were imaged in upright and supine positions using an upright MRI. The cranio-caudal and caudo-cranial CSF flow, velocity and stroke volume were measured at the C2 spinal level over one cardiac cycle using phase contrast MRI. Statistical analysis was performed to identify differences in CSF flow properties between the two positions., Results: CSF stroke volume per cardiac cycle, representing CSF volume oscillating in and out of the cranium, was ~ 57.6% greater in supine (p < 0.0001), due to a ~ 83.8% increase in caudo-cranial CSF peak velocity during diastole (p < 0.0001) and extended systolic phase duration when moving from upright (0.25 ± 0.05 s) to supine (0.34 ± 0.08 s; p < 0.0001). Extrapolation to a 24 h timeframe showed significantly larger total CSF volume exchanged at C2 with 10 h spent supine versus only 5 h (p < 0.0001)., Conclusions: In summary, body position has significant effects on CSF flow in and out of the cranium, with more CSF oscillating in supine compared to upright position. Such difference was driven by an increased caudo-cranial diastolic CSF velocity and an increased systolic phase duration when moving from upright to supine position. Extrapolation to a 24 h timeframe suggests that more time spent in supine position increases total amount of CSF exchange, which may play a beneficial role in waste clearance in the brain., (© 2021. The Author(s).)