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Background and Purpose: Conclusions from prior literature regarding the impact of sex, age, and height on spinal cord (SC) MRI morphometrics are conflicting, while the effect of body weight on SC morphometrics has been found to be nonsignificant. The purpose of this case-control study is to assess the associations between cervical SC MRI morphometric parameters and age, sex, height, and weight to establish their potential role as confounding variables in a clinical study of people with multiple sclerosis (MS) compared to a cohort of healthy volunteers., Methods: Sixty-nine healthy volunteers and 31 people with MS underwent cervical SC MRI at 3 Tesla field strength. Images were centered at the C3/C4 intervertebral disc and processed using Spinal Cord Toolbox v.4.0.2. Mixed-effects linear regression models were used to evaluate the effects of biological variables and disease status on morphometric parameters., Results: Sex, age, and height had significant effects on cord and gray matter (GM) cross-sectional area (CSA) as well as the GM:cord CSA ratio. There were no significant effects of body weight on morphometric parameters. The effect of MS disease duration on cord CSA in the C4 level was significant when controlling for all other variables., Conclusions: Studies of disease-related changes in SC morphometry should control for sex, age, and height to account for physiological variation., (© 2024 The Author(s). Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation of α-synuclein protofibrils. New diagnostic methods assess α-synuclein aggregation characteristics from cerebrospinal fluid (CSF) and recent pathophysiologic mechanisms suggest that CSF circulation disruptions may precipitate α-synuclein retention. Here, diffusion-weighted MRI with low-to-intermediate diffusion-weightings was applied to test the hypothesis that CSF motion is reduced in Parkinson's disease relative to healthy participants., Methods: Multi-shell diffusion weighted MRI (spatial resolution = 1.8 × 1.8 × 4.0 mm) with low-to-intermediate diffusion weightings (b-values = 0, 50, 100, 200, 300, 700, and 1000 s/mm 2 ) was applied over the approximate kinetic range of suprasellar cistern fluid motion at 3 Tesla in Parkinson's disease (n = 27; age = 66 ± 6.7 years) and non-Parkinson's control (n = 32; age = 68 ± 8.9 years) participants. Wilcoxon rank-sum tests were applied to test the primary hypothesis that the noise floor-corrected decay rate of CSF signal as a function of b-value, which reflects increasing fluid motion, is reduced within the suprasellar cistern of persons with versus without Parkinson's disease and inversely relates to choroid plexus activity assessed from perfusion-weighted MRI (significance-criteria: p < 0.05)., Results: Consistent with the primary hypothesis, CSF decay rates were higher in healthy (D = 0.00673 ± 0.00213 mm 2 /s) relative to Parkinson's disease (D = 0.00517 ± 0.00110 mm 2 /s) participants. This finding was preserved after controlling for age and sex and was observed in the posterior region of the suprasellar cistern (p < 0.001). An inverse correlation between choroid plexus perfusion and decay rate in the voxels within the suprasellar cistern (Spearman's-r=-0.312; p = 0.019) was observed., Conclusions: Multi-shell diffusion MRI was applied to identify reduced CSF motion at the level of the suprasellar cistern in adults with versus without Parkinson's disease; the strengths and limitations of this methodology are discussed in the context of the growing literature on CSF flow., (© 2024. The Author(s).)

Background: The choroid plexus functions as the blood-cerebrospinal fluid (CSF) barrier, plays an important role in CSF production and circulation, and has gained increased attention in light of the recent elucidation of CSF circulation dysfunction in neurodegenerative conditions. However, methods for routinely quantifying choroid plexus volume are suboptimal and require technical improvements and validation. Here, we propose three deep learning models that can segment the choroid plexus from commonly-acquired anatomical MRI data and report performance metrics and changes across the adult lifespan., Methods: Fully convolutional neural networks were trained from 3D T 1 -weighted, 3D T 2 -weighted, and 2D T 2 -weighted FLAIR MRI using gold-standard manual segmentations in control and neurodegenerative participants across the lifespan (n = 50; age = 21-85 years). Dice coefficients, 95% Hausdorff distances, and area-under-curve (AUCs) were calculated for each model and compared to segmentations from FreeSurfer using two-tailed Wilcoxon tests (significance criteria: p < 0.05 after false discovery rate multiple comparisons correction). Metrics were regressed against lateral ventricular volume using generalized linear models to assess model performance for varying levels of atrophy. Finally, models were applied to an expanded cohort of adult controls (n = 98; age = 21-89 years) to provide an exemplar of choroid plexus volumetry values across the lifespan., Results: Deep learning results yielded Dice coefficient = 0.72, Hausdorff distance = 1.97 mm, AUC = 0.87 for T 1 -weighted MRI, Dice coefficient = 0.72, Hausdorff distance = 2.22 mm, AUC = 0.87 for T 2 -weighted MRI, and Dice coefficient = 0.74, Hausdorff distance = 1.69 mm, AUC = 0.87 for T 2 -weighted FLAIR MRI; values did not differ significantly between MRI sequences and were statistically improved compared to current commercially-available algorithms (p < 0.001). The intraclass coefficients were 0.95, 0.95, and 0.96 between T 1 -weighted and T 2 -weighted FLAIR, T 1 -weighted and T 2 -weighted, and T 2 -weighted and T 2 -weighted FLAIR models, respectively. Mean lateral ventricle choroid plexus volume across all participants was 3.20 ± 1.4 cm 3 ; a significant, positive relationship (R 2  = 0.54-0.60) was observed between participant age and choroid plexus volume for all MRI sequences (p < 0.001)., Conclusions: Findings support comparable performance in choroid plexus delineation between standard, clinically available, non-contrasted anatomical MRI sequences. The software embedding the evaluated models is freely available online and should provide a useful tool for the growing number of studies that desire to quantitatively evaluate choroid plexus structure and function ( https://github.com/hettk/chp&#95;seg )., (© 2024. The Author(s).)

Background: Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid (CSF) egress and neuroimmune surveillance. Neurofluid circulation dysfunction may manifest as morphological changes in these structures, however, automated quantification of these structures is not possible and rather characterization often requires exogenous contrast agents and manual delineation., Methods: We propose a deep learning architecture to automatically delineate the peri-sinus space (e.g., PSD and intravenous AG structures) using two cascaded 3D fully convolutional neural networks applied to submillimeter 3D T 2 -weighted non-contrasted MRI images, which can be routinely acquired on all major MRI scanner vendors. The method was evaluated through comparison with gold-standard manual tracing from a neuroradiologist (n = 80; age range = 11-83 years) and subsequently applied in healthy participants (n = 1,872; age range = 5-100 years), using data from the Human Connectome Project, to provide exemplar metrics across the lifespan. Dice-Sørensen and a generalized linear model was used to assess PSD and AG changes across the human lifespan using quadratic restricted splines, incorporating age and sex as covariates., Results: Findings demonstrate that the PSD and AG volumes can be segmented using T 2 -weighted MRI with a Dice-Sørensen coefficient and accuracy of 80.7 and 74.6, respectively. Across the lifespan, we observed that total PSD volume increases with age with a linear interaction of gender and age equal to 0.9 cm 3 per year (p < 0.001). Similar trends were observed in the frontal and parietal, but not occipital, PSD. An increase in AG volume was observed in the third to sixth decades of life, with a linear effect of age equal to 0.64 mm 3 per year (p < 0.001) for total AG volume and 0.54 mm 3 (p < 0.001) for maximum AG volume., Conclusions: A tool that can be applied to quantify PSD and AG volumes from commonly acquired T 2 -weighted MRI scans is reported and exemplar volumetric ranges of these structures are provided, which should provide an exemplar for studies of neurofluid circulation dysfunction. Software and training data are made freely available online ( https://github.com/hettk/spesis )., (© 2024. The Author(s).)

Background and Purpose: Paramagnetic rims and the central vein sign (CVS) are proposed imaging markers of multiple sclerosis (MS) lesions. Using 7 tesla magnetic resonance imaging, we aimed to: (1) characterize the appearance of paramagnetic rim lesions (PRLs); (2) assess whether PRLs and the CVS are associated with higher levels of MS pathology; and (3) compare the characteristics between subjects with and without PRLs in early MS., Methods: Prospective study of 32 treatment-naïve subjects around the time of diagnosis who were assessed for the presence of PRLs and the CVS. Comparisons of lesion volume and macromolecular pool size ratio (PSR) index, a proxy of myelin integrity, between PRLs and non-PRLs, and CVS-positive and CVS-negative lesions were carried out. Differences in clinical/demographic characteristics between patients with PRLs and those without were tested., Results: Fifteen subjects had ≥1 PRL for a total of 36 PRLs, of which two-thirds had a full rim. PRLs predicted a larger lesion size and decreased PSR signal. Lesion volume and presence of cervical spine lesions were significantly different between subjects with PRLs and those without, although neither remained significant after adjusting for multiple comparisons. One hundred and eighty-one lesions with CVS were identified with no differences between CVS-positive and CVS-negative lesions in volume (p = .27) and PSR values (p = .62)., Conclusions: PRLs, but not CVS-positive lesions, are larger and have lower myelin integrity. Our findings indicate that PRLs are associated with higher levels of lesion-specific pathology prior to the start of disease-modifying therapy., (© 2023 American Society of Neuroimaging.)

Background and Purpose: Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy., Methods: We performed hypercapnic reactivity (blood oxygenation level-dependent; echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm, repetition time = 2000 ms) and catheter angiography assessments of ChP reserve capacity and vascular patency in moyamoya patients (n = 53) with and without prior surgical revascularization. Time regression analyses quantified maximum cerebrovascular reactivity and reactivity delay time in ChP and cortical flow territories of major intracranial vessels with steno-occlusion graded as <70%, 70%-99%, and occlusion using Warfarin-Aspirin-Symptomatic-Intracranial-Disease stenosis grading criteria. Analysis of variance (significance: two-sided Bonferroni-corrected p < .05) was applied to evaluate cortical and ChP reactivity, after accounting for end-tidal carbon dioxide change, for differing vasculopathy categories., Results: In patients without prior revascularization, arterial vasculopathy was associated with reduced cortical reactivity and lengthened reactivity delay (p ≤ .01), as expected. Regardless of surgical history, the ChP reactivity metrics were not significantly related to the degree of proximal stenosis, consistent with ChP reactivity being largely preserved in this population., Conclusions: Findings are consistent with ChP reactivity in moyamoya not being dependent on observed vasculopathy. Future work may investigate the extent to which ChP hyperemia in chronic ischemia reflects circulating markers of glial or ischemic stress., (© 2023 American Society of Neuroimaging.)

Background: Susceptibility-weighted imaging (SWI) has been extensively studied in the brain and in diseases of the central nervous system such as multiple sclerosis (MS) providing unique opportunities to visualize cerebral vasculature and disease-related pathology, including the central vein sign (CVS) and paramagnetic rim lesions (PRLs). However, similar studies evaluating SWI in the spinal cord of patients with MS remain severely limited., Purpose: Based on our previous findings of enlarged spinal vessels in MS compared to healthy controls (HCs), we developed high-field SWI acquisition and processing methods for the cervical spinal cord with application in people with MS (pwMS) and HCs. Here, we demonstrate the vascular variability between the two cohorts and unique MS lesion features in the cervical cord., Methods: In this retrospective, exploratory pilot study conducted between March 2021 and March 2022, we scanned 12 HCs and 9 pwMS using an optimized non-contrast 2D T2*-weighted gradient echo sequence at 7 tesla. The overall appearance of the white and gray matter as well as tissue vasculature were compared between the two cohorts and areas of MS pathology in the patient group were assessed using both the magnitude and processed SWI images., Results: We show improved visibility of vessels and more pronounced gray and white matter contrast in the MS group compared to HCs, hypointensities surrounding the cord in the MS cohort, and identify signal changes indicative of the CVS and paramagnetic rims in 66 % of pwMS with cervical spinal lesions., Conclusion: In this first study of SWI at 7T in the human spinal cord, SWI holds promise in advancing our understanding of disease processes in the cervical cord in MS., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: Imaging investigation of cerebrospinal fluid (CSF) in multiple sclerosis (MS) is understudied. Development of noninvasive methods to detect pathological CSF changes would have a profound effect on MS diagnosis and would offer insight into MS pathophysiology and mechanisms of neurological impairment., Objective: We propose magnetization transfer (MT) MRI as a tool to detect macromolecular changes in spinal CSF., Methods: MT and quantitative MT (qMT) data were acquired in the cervical region in 27 people with relapsing-remitting multiple sclerosis (pwRRMS) and 38 age and sex-matched healthy controls (HCs). MT ratio (MTR), the B 1 , B 0 , and R 1 corrected qMT-derived pool size ratio (PSR) were quantified in the spinal cord and CSF of each group., Results: Both CSF MTR and CSF qMT-derived PSR were significantly increased in pwRRMS compared to HC ( p  = 0.027 and p  = 0.020, respectively). CSF PSR of pwRRMS was correlated to Expanded Disability Status Scale Scores ( p  = 0.045, R = 0.352)., Conclusion: Our findings demonstrate increased CSF macromolecular content in pwRRMS and link CSF macromolecular content with clinical impairment. This highlights the potential role of CSF in processing products of demyelination., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Objective: Investigations of cerebrospinal fluid (CSF) flow aberrations in Huntington's disease (HD) are of growing interest, as impaired CSF flow may contribute to mutant Huntington retention and observed heterogeneous responsiveness to intrathecally administered therapies., Method: We assessed net cerebral aqueduct CSF flow and velocity in 29 HD participants (17 premanifest and 12 manifest) and 51 age- and sex matched non-HD control participants using 3-Tesla magnetic resonance imaging methods. Regression models were applied to test hypotheses regarding: (i) net CSF flow and cohort, (ii) net CSF flow and disease severity (CAP-score), and (iii) CSF volume after correcting for age and sex., Results: Group-wise analyses support a decrease in net CSF flow in HD (mean 0.14 ± 0.27 mL/min) relative to control (mean 0.32 ± 0.20 mL/min) participants (p = 0.02), with lowest flow in the manifest HD cohort (mean 0.04 ± 0.25 mL/min). This finding was explained by hyperdynamic CSF movement, manifesting as higher caudal systolic CSF flow velocity and higher diastolic cranial CSF flow velocity across the cardiac cycle, in HD (caudal flow: 0.17 ± 0.07 mL/s, cranial flow: 0.14 ± 0.08 mL/s) compared to control (caudal flow: 0.13 ± 0.06 mL/s, cranial flow: 0.11 ± 0.04 mL/s) participants. A positive correlation between cranial diastolic flow and disease severity was observed (p = 0.02)., Interpretations: Findings support aqueductal CSF flow dynamics changing with disease severity in HD. These accelerated changes are consistent with changes observed over the typical adult lifespan, and may have relevance to mutant Huntington retention and intrathecally administered therapeutics responsiveness. ANN NEUROL 2023;94:885-894., (© 2023 American Neurological Association.)

Functional MRI (fMRI) of the spinal cord is an expanding area of research with potential to investigate neuronal activity in the central nervous system. We aimed to characterize the functional connectivity features of the human lumbar spinal cord using resting-state fMRI (rs-fMRI) at 3T, using region-based and data-driven analysis approaches. A 3D multi-shot gradient echo resting-state blood oxygenation level dependent-sensitive rs-fMRI protocol was implemented in 26 healthy participants. Average temporal signal-to-noise ratio in the gray matter was 16.35 ± 4.79 after denoising. Evidence of synchronous signal fluctuations in the ventral and dorsal horns with their contralateral counterparts was observed in representative participants using interactive, exploratory seed-based correlations. Group-wise average in-slice Pearson's correlations were 0.43 ± 0.17 between ventral horns, and 0.48 ± 0.16 between dorsal horns. Group spatial independent component analysis (ICA) was used to identify areas of coherent activity¸ and revealed components within the gray matter corresponding to anatomical regions. Lower-dimensionality ICA revealed bilateral components corresponding to ventral and dorsal networks. Additional separate ICAs were run on two subsets of the participant group, yielding two sets of components that showed visual consistency and moderate spatial overlap. This work shows feasibility of rs-fMRI to probe the functional features and organization of the lumbar spinal cord., (© 2023. Springer Nature Limited.)

One of the pathological hallmarks of Alzheimer's and related diseases is the increased accumulation of protein amyloid-β in the brain parenchyma. As such, recent studies have focused on characterizing protein and related clearance pathways involving perivascular flow of neurofluids, but human studies of these pathways are limited owing to limited methods for evaluating neurofluid circulation non-invasively in vivo . Here, we utilize non-invasive MRI methods to explore surrogate measures of CSF production, bulk flow and egress in the context of independent PET measures of amyloid-β accumulation in older adults. Participants ( N = 23) were scanned at 3.0 T with 3D T 2 -weighted turbo spin echo, 2D perfusion-weighted pseudo-continuous arterial spin labelling and phase-contrast angiography to quantify parasagittal dural space volume, choroid plexus perfusion and net CSF flow through the aqueduct of Sylvius, respectively. All participants also underwent dynamic PET imaging with amyloid-β tracer 11 C-Pittsburgh Compound B to quantify global cerebral amyloid-β accumulation. Spearman's correlation analyses revealed a significant relationship between global amyloid-β accumulation and parasagittal dural space volume (rho = 0.529, P = 0.010), specifically in the frontal (rho = 0.527, P = 0.010) and parietal (rho = 0.616, P = 0.002) subsegments. No relationships were observed between amyloid-β and choroid plexus perfusion nor net CSF flow. Findings suggest that parasagittal dural space hypertrophy, and its possible role in CSF-mediated clearance, may be closely related to global amyloid-β accumulation. These findings are discussed in the context of our growing understanding of the physiological mechanisms of amyloid-β aggregation and clearance via neurofluids., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The choroid plexus (ChP) comprises a collection of modified ependymal cells that play an important role in the production of brain cerebrospinal fluid (CSF), and ChP perfusion aberrations have been implicated in a range of cerebrovascular and neurodegenerative disorders. To provide an exemplar for the growing interest in ChP activity, we evaluated ChP perfusion and bulk CSF flow cross-sectionally across the healthy adult lifespan. Participants (n = 77; age range = 21-86 years) were scanned at 3T using T 1 -weighted, T 2 -weighted-FLAIR, perfusion-weighted pCASL, and phase contrast MRI to calculate ChP anatomy, perfusion, and aqueductal CSF flow, respectively. Regression models were applied to evaluate aging effects on ChP volume and ChP perfusion in the lateral ventricles, as well as CSF flow. ChP volume (mean ± std = 2.81 ± 1.1 cm 3 ) increased (p < 0.001), ChP perfusion (36.3 ± 8.6 mL/100 g/min) decreased (p = 0.0078), and ChP total blood flow (1.13 ± 0.34 mL/min) increased (p < 0.001) with age. Cranial-to-caudal net CSF flow (0.245 ± 0.20 mL/min) decreased, absolute CSF flow (4.86 ± 2.96 mL/min) increased, and CSF regurgitant fraction (0.87 ± 0.126) increased with age (all: p < 0.001). ChP perfusion was directly related to net cranial-to-caudal CSF flow through the aqueduct (p = 0.033). The implications of these findings are discussed in the context of the growing literature on CSF circulatory dysfunction in neurodegeneration and cerebrovascular disease.

Quantitative diffusion MRI (dMRI) is a promising technique for evaluating the spinal cord in health and disease. However, low signal-to-noise ratio (SNR) can impede interpretation and quantification of these images. The purpose of this study is to evaluate several dMRI denoising approaches on their ability to improve the quality, reliability, and accuracy of quantitative diffusion MRI of the spinal cord. We evaluate three denoising approaches (Non-Local Means, Marchenko-Pastur PCA, and a newly proposed Patch2Self algorithm) and conduct five experiments to validate the denoising performance on clinical-quality and commonly-acquired dMRI acquisitions: 1) a phantom experiment to assess denoising error and bias; 2) a multi-vendor, multi-acquisition open experiment for both qualitative and quantitative evaluation of noise residuals; 3) a bootstrapping experiment to estimate uncertainty of parametric maps; 4) an assessment of spinal cord lesion conspicuity in a multiple sclerosis group; and 5) an evaluation of denoising for advanced parametric multi-compartment modeling. We find that all methods improve signal-to-noise ratio and conspicuity of MS lesions in individual diffusion weighted images (DWIs), but MPPCA and Patch2Self excel at improving the quality and intra-cord contrast of diffusion weighted images - removing signal fluctuations due to thermal noise while improving precision of estimation of diffusion parameters even with very few DWIs (i.e., 16-32) typical of clinical acquisitions. These denoising approaches hold promise for facilitating reliable diffusion observations and measurements in the spinal cord to investigate biological and pathological processes., (Copyright © 2022. Published by Elsevier Inc.)

Background: It remains a clinical challenge to differentiate brain tumors from radiation-induced necrosis in the brain. Despite significant improvements, no single MRI method has been validated adequately in the clinical setting., Methods: Multi-parametric MRI (mpMRI) was performed to differentiate 9L gliosarcoma from radiation necrosis in animal models. Five types of MRI methods probed complementary information on different scales i.e., T 2 (relaxation), CEST based APT (probing mobile proteins/peptides) and rNOE (mobile macromolecules), qMT (macromolecules), diffusion based ADC (cell density) and SSIFT iAUC (cell size), and perfusion based DSC (blood volume and flow)., Results: For single MRI parameters, iAUC and ADC provide the best discrimination of radiation necrosis and brain tumor. For mpMRI, a combination of iAUC, ADC, and APT shows the best classification performance based on a two-step analysis with the Lasso and Ridge regressions., Conclusion: A general mpMRI approach is introduced to choosing candidate multiple MRI methods, identifying the most effective parameters from all the mpMRI parameters, and finding the appropriate combination of chosen parameters to maximize the classification performance to differentiate tumors from radiation necrosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Brain metastasis is a common characteristic of late-stage lung cancers. High doses of targeted radiotherapy can control tumor growth in the brain but can also result in radiotherapy-induced necrosis. Current methods are limited for distinguishing whether new parenchymal lesions following radiotherapy are recurrent tumors or radiotherapy-induced necrosis, but the clinical management of these two classes of lesions differs significantly. Here, we developed, validated, and evaluated a new MRI technique termed selective size imaging using filters via diffusion times (SSIFT) to differentiate brain tumors from radiotherapy necrosis in the brain. This approach generates a signal filter that leverages diffusion time dependence to establish a cell size-weighted map. Computer simulations in silico, cultured cancer cells in vitro, and animals with brain tumors in vivo were used to comprehensively validate the specificity of SSIFT for detecting typical large cancer cells and the ability to differentiate brain tumors from radiotherapy necrosis. SSIFT was also implemented in patients with metastatic brain cancer and radiotherapy necrosis. SSIFT showed high correlation with mean cell sizes in the relevant range of less than 20 μm. The specificity of SSIFT for brain tumors and reduced contrast in other brain etiologies allowed SSIFT to differentiate brain tumors from peritumoral edema and radiotherapy necrosis. In conclusion, this new, cell size-based MRI method provides a unique contrast to differentiate brain tumors from other pathologies in the brain., Significance: This work introduces and provides preclinical validation of a new diffusion MRI method that exploits intrinsic differences in cell sizes to distinguish brain tumors and radiotherapy necrosis., (©2022 American Association for Cancer Research.)

Background: Recent studies have suggested alternative cerebrospinal fluid (CSF) clearance pathways for brain parenchymal metabolic waste products. One fundamental but relatively under-explored component of these pathways is the anatomic region surrounding the superior sagittal sinus, which has been shown to have relevance to trans-arachnoid molecular passage. This so-called parasagittal dural (PSD) space may play a physiologically significant role as a distal intracranial component of the human glymphatic circuit, yet fundamental gaps persist in our knowledge of how this space changes with normal aging and intracranial bulk fluid transport., Methods: We re-parameterized MRI methods to assess CSF circulation in humans using high resolution imaging of the PSD space and phase contrast measures of flow through the cerebral aqueduct to test the hypotheses that volumetric measures of PSD space (1) are directly related to CSF flow (mL/s) through the cerebral aqueduct, and (2) increase with age. Multi-modal 3-Tesla MRI was applied in healthy participants (n = 62; age range = 20-83 years) across the adult lifespan whereby phase contrast assessments of CSF flow through the aqueduct were paired with non-contrasted T 1 -weighted and T 2 -weighted MRI for PSD volumetry. PSD volume was extracted using a recently validated neural networks algorithm. Non-parametric regression models were applied to evaluate how PSD volume related to tissue volume and age cross-sectionally, and separately how PSD volume related to CSF flow (significance criteria: two-sided p < 0.05)., Results: A significant PSD volume enlargement in relation to normal aging (p < 0.001, Spearman's-[Formula: see text] = 0.6), CSF volume (p < 0.001, Spearman's-[Formula: see text] = 0.6) and maximum CSF flow through the aqueduct of Sylvius (anterograde and retrograde, p < 0.001) were observed. The elevation in PSD volume was not significantly related to gray or white matter tissue volumes. Findings are consistent with PSD volume increasing with age and bulk CSF flow., Conclusions: Findings highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Additionally, findings demonstrate that PSD volume increases with age and relates to CSF volume and bi-directional flow. Values reported should provide useful normative ranges for how PSD volume adjusts with age, which will serve as a necessary pre-requisite for comparisons to persons with neurodegenerative disorders., (© 2022. The Author(s).)

Focal lesions may affect functional connectivity (FC) of the ventral and dorsal networks in the cervical spinal cord of people with relapsing-remitting multiple sclerosis (RRMS). Resting-state FC can be measured using functional MRI (fMRI) at 3T. This study sought to determine whether alterations in FC may be related to the degree of damage in the normal-appearing tissue. Tissue integrity and FC in the cervical spinal cord were assessed with diffusion tensor imaging (DTI) and resting-state fMRI, respectively, in a group of 26 RRMS participants with high cervical lesion load, low disability, and minimally impaired sensorimotor function, and healthy controls. Lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in the normal-appearing white matter in the RRMS group relative to controls. Average FC in ventral and dorsal networks was similar between groups. Significant associations were found between higher FC in the dorsal sensory network and several DTI markers of pathology in the normal-appearing tissue. In the normal-appearing grey matter, dorsal FC was positively correlated with axial diffusivity (AD) (r = 0.46, p = 0.020) and mean diffusivity (MD) (r = 0.43, p = 0.032). In the normal-appearing white matter, dorsal FC was negatively correlated with FA (r = -0.43, p = 0.028) and positively correlated with RD (r = 0.49, p = 0.012), AD (r = 0.42, p = 0.037) and MD (r = 0.53, p = 0.006). These results suggest that increased connectivity, while remaining within the normal range, may represent a compensatory mechanism in response to structural damage in support of preserved sensory function in RRMS., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The Radiology Research Alliance (RRA) of the Association of University Radiologists (AUR) convenes Task Forces to address current topics in radiology. In this article, the AUR-RRA Task Force on Academic-Industry Partnerships for Artificial Intelligence, considered issues of importance to academic radiology departments contemplating industry partnerships in artificial intelligence (AI) development, testing and evaluation. Our goal was to create a framework encompassing the domains of clinical, technical, regulatory, legal and financial considerations that impact the arrangement and success of such partnerships., (Copyright © 2021 The Association of University Radiologists. All rights reserved.)

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process., (Copyright © 2021. Published by Elsevier Inc.)

Cerebrospinal fluid (CSF) and interstitial fluid exchange have been shown to increase following pharmacologically-manipulated increases in cerebral arterial pulsatility, consistent with arterial pulsatility improving CSF circulation along perivascular glymphatic pathways. The choroid plexus (CP) complexes produce CSF, and CP activity may provide a centralized indicator of perivascular flow. We tested the primary hypothesis that elevated cortical cerebral blood volume and flow, present in sickle cell disease (SCD), is associated with fractionally-reduced CP perfusion relative to healthy adults, and the supplementary hypothesis that reduced arterial patency, present in moyamoya vasculopathy, is associated with elevated fractional CP perfusion relative to healthy adults. Participants (n = 75) provided informed consent and were scanned using a 3-Tesla arterial-spin-labeling MRI sequence for CP and cerebral gray matter (GM) perfusion quantification. ANOVA was used to calculate differences in CP-to-GM perfusion ratios between groups, and regression analyses applied to evaluate the dependence of the CP-to-GM perfusion ratio on group after co-varying for age and sex. ANOVA yielded significant (p < 0.001) group differences, with CP-to-GM perfusion ratios increasing between SCD (ratio = 0.93 ± 0.28), healthy (ratio = 1.04 ± 0.32), and moyamoya (ratio = 1.29 ± 0.32) participants, which was also consistent with regression analyses. Findings are consistent with CP perfusion being inversely associated with cortical perfusion.

Background: Reduced diffusion along perivascular spaces in adults with Alzheimer's-disease-related-dementias has been reported and attributed to reduced glymphatic function., Objectives: To apply quantitative measures of diffusion along, and orthogonal to, perivascular spaces in a cohort of older adults with and without clinical symptoms of alpha-synuclein related neurodegeneration., Methods: 181 adults with Parkinson disease (PD) or essential tremor (ET) additionally sub-classified by the presence of cognitive impairment underwent 3 T MRI. Diffusion-tensor-imaging (spatial resolution = 2x2x2 mm; b-value = 1000 s/mm 2 ; directions = 33) measures of diffusion (mm 2 /s) parallel and orthogonal to perivascular spaces at the level of the medullary veins, and the ratio of these measures (ALPS-index), were calculated. Regions were identified by a board-certified neuroradiologist from T 1 -weighted and T 2 -weighted MRI. Evaluations of motor impairment and mild cognitive impairment (MCI) were interpreted by a board-certified neurologist and neuropsychologist, respectively. Multiple regression with false discovery rate correction was applied to understand how diffusion metrics related to (i) disease category (PD vs. ET), (ii) cognition (MCI status), and (iii) white matter disease severity from the Fazekas score., Results: The ALPS-index was reduced in PD compared to ET participants (p = 0.037). No association between the ALPS-index and MCI status, but an inverse association between the ALPS-index and Fazekas score (p = 0.002), was observed. The ALPS-index was inversely associated with age (p = 0.007)., Conclusion: Diffusion aberrations near perivascular spaces are evident in patients with alpha-synuclein related neurodegenerative disorders, and are related to age and white matter disease severity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose of Review: The glymphatic system is a relatively new concept that has been associated with regulation of cerebrospinal fluid (CSF), as well as brain waste clearance. Novel techniques to study glymphatic dysfunction have in turn prompted a reassessment of brain physiology and underlying elements of neurological disease. This review incorporates a contemporary imaging perspective focused on understanding the regulation of CSF flow, thus expanding the putative clinical relevance of this system and the relationships between CSF flow and glymphatic function., Recent Findings: MR imaging studies, especially those that employ intrathecal gadolinium contrast, have identified potentially new pathways regulating CSF production, absorption, and clearance. These studies, when viewed in the context of more historical anatomic descriptors of CSF production and absorption, provide a more robust description of CSF physiology and waste clearance. CSF production and resorption are under-investigated and could be related to various pathophysiologic processes in neurodegeneration. Anatomically based clinical exemplars of CSF clearance are discussed. Future studies should focus on linking glymphatic functionality with neurological disease.

Physician education occurs through two mechanisms that operate in tandem: the explicit and the implicit curriculum. The explicit, or formal, curriculum is the official version that is usually taken as the one-and-only curriculum and which is detailed in official documentation; however, an implicit curriculum exists, comprised of subtle messaging about professional norms, values, and beliefs that are tacitly communicated through both positive and negative role modeling. Both contribute to the overall education of the medical student and physician-in-training. Despite its well-documented influence in medical education, much of the teachings of the implicit curriculum occurs in the shadows, unspoken and unarticulated, and outside the awareness of both teacher and student. As panel members of the The Implicit Curriculum in Radiology Task Force of the Association of University Radiologists-Radiology Research Alliance (AUR-RRA), we present a review of the implicit curriculum, exploring its origin and impact on medical education, and on the overall professional development of medical students, post-graduate medical trainees and practicing physicians. Strategies for recognizing and contending with the implicit curriculum in radiology training are discussed, with a special emphasis on opportunities to leverage its potential through positive role modeling., Competing Interests: Declaration of Competing Interest The authors claim no potential conflict of interest., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Recent studies have provided evidence that cortical brain ischemia may influence choroid plexus function, and such communication may be mediated by either traditional CSF circulation pathways and/or a possible glymphatic pathway. Here we investigated the hypothesis that improvements in arterial health following neoangiogenesis alter (i) intracranial CSF volume and (ii) choroid plexus perfusion in humans. CSF and tissue volume measurements were obtained from T 1 -weighted MRI, and cortical and choroid plexus perfusion were obtained from perfusion-weighted arterial spin labeling MRI, in patients with non-atherosclerotic intracranial stenosis (e.g. Moyamoya). Measurements were repeated after indirect surgical revascularization, which elicits cortical neoangiogenesis near the revascularization site ( n  = 23; age = 41.8 ± 13.4 years), or in a cohort of participants at two time points without interval surgeries ( n  = 10; age = 41.7 ± 10.7 years). Regression analyses were used to evaluate dependence of perfusion and volume on state (time 1 vs. 2). Post-surgery, neither CSF nor tissue volumes changed significantly. In surgical patients, cortical perfusion increased and choroid plexus perfusion decreased after surgery; in participants without surgeries, cortical perfusion reduced and choroid plexus perfusion increased between time points. Findings are discussed in the context of a homeostatic mechanism, whereby arterial health, paravascular flow, and/or ischemia can affect choroid plexus perfusion.

Objective: This study explores the relationship between health access barriers and diabetes in an urban First Nations population in Canada., Design: Data from a self-identified urban First Nations population were collected using respondent-driven sampling (RDS). As no clear approach for regression modelling of RDS data is available, two logistic regression modelling approaches, including survey-based logistic and generalised linear mixed models, were used to explore the relationship between diabetes and health barriers of interest, including access to healthcare, food, housing and socioeconomic factors., Setting: Hamilton, Ontario, Canada., Participants: This cross-sectional study used data collected from the Our Health Counts study, in partnership with the De dwa da dehs nye>s Aboriginal Health Centre, which recruited 554 First Nations adults living in Hamilton using RDS., Results: After adjusting for covariates, multivariable regression techniques showed a statistically significant relationship between a self-reported diagnosis of diabetes and a lack of culturally appropriate care among urban First Nations peoples (OR: 12.70, 95% CI 2.52 to 57.91). There was also a trend towards a relationship between diabetes and not having a doctor available in the area, feeling that healthcare provided was inadequate and a lack of available healthcare services in the area., Conclusions: Urban First Nations peoples who felt the health service they received was not culturally appropriate were more likely to have diabetes, compared with those who did not feel the service they received was culturally inappropriate. Establishing more healthcare services that integrate First Nations cultures and traditions could improve access to care and the course of treatment for urban First Nations peoples living with diabetes., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: A modern imaging review is necessary to further define the anatomic origin of the juvenile nasopharyngeal angiofibroma., Methods: After institutional review board approval, a search from January 1998 to January 2013 yielded 33 male patients (aged 10-23 years) with pathologically proven juvenile nasopharyngeal angiofibroma lesions, as well as pretreatment computed tomography/magnetic resonance imaging. Juvenile nasopharyngeal angiofibroma involvement was assessed in the following regions: sphenopalatine foramen, pterygopalatine fossa, vidian canal, nasopharynx, nasal cavity, sphenoid sinus, choana, pterygomaxillary fissure/masticator space, orbit, and sphenoid bone., Results: The choana and nasopharynx were involved in all 33 patients. In contrast, only 22 lesions involved the pterygopalatine fossa, 24 lesions involved the sphenopalatine foramen, and 28 lesions involved the vidian canal., Conclusions: Our results suggest that the juvenile nasopharyngeal angiofibroma origin is in the region of the choana and nasopharynx rather than the sphenopalatine foramen or pterygopalatine fossa.

Rationale and Objectives: Infectious encephalitis is a relatively common cause of morbidity and mortality. Treatment of infectious encephalitis with antiviral medication can be highly effective when administered promptly. Clinical mimics of encephalitis arise from a broad range of pathologic processes, including toxic, metabolic, neoplastic, autoimmune, and cardiovascular etiologies. These mimics need to be rapidly differentiated from infectious encephalitis to appropriately manage the correct etiology; however, the many overlapping signs of these various entities present a challenge to accurate diagnosis. A systematic approach that considers both the clinical manifestations and the imaging findings of infectious encephalitis and its mimics can contribute to more accurate and timely diagnosis., Materials and Methods: Following an institutional review board approval, a health insurance portability and accountability act (HIPAA)-compliant search of our institutional imaging database (teaching files) was conducted to generate a list of adult and pediatric patients who presented between January 1, 1995 and October 10, 2013 for imaging to evaluate possible cases of encephalitis. Pertinent medical records, including clinical notes as well as surgical and pathology reports, were reviewed and correlated with imaging findings. Clinical and imaging findings were combined to generate useful flowcharts designed to assist in distinguishing infectious encephalitis from its mimics. Key imaging features were reviewed and were placed in the context of the provided flowcharts., Results: Four flowcharts were presented based on the primary anatomic site of imaging abnormality: group 1: temporal lobe; group 2: cerebral cortex; group 3: deep gray matter; and group 4: white matter. An approach that combines features on clinical presentation was then detailed. Imaging examples were used to demonstrate similarities and key differences., Conclusions: Early recognition of infectious encephalitis is critical, but can be quite complex due to diverse pathologies and overlapping features. Synthesis of both the clinical and imaging features of infectious encephalitis and its mimics is critical to a timely and accurate diagnosis. The use of the flowcharts presented in this article can further enable both clinicians and radiologists to more confidently differentiate encephalitis from its mimics and improve patient care., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this article is to present imaging approaches and key technical, safety, and patient care best practices critical for safe, successful image-guided biopsy of head and neck masses., Conclusion: Image-guided sampling is an important adjunct to the diagnosis and management of head and neck masses and may be particularly useful when lesions are not accessible via an endoscope or by palpation-guided sampling. Appropriate workup is mandatory before the patient is scheduled for such a procedure. Once the procedure has been initiated, needle selection and technique are critical for increasing the diagnostic yield. Knowledge of the various head and neck biopsy approaches and their associated complications is important for optimal tissue sampling and minimization of morbidity.

Background: Over the last decade there has been escalating concern regarding the increasing radiation exposure stemming from CT exams, particularly in children. Adaptive statistical iterative reconstruction (ASIR) is a relatively new and promising tool to reduce radiation dose while preserving image quality. While encouraging results have been found in adult head and chest and body imaging, validation of this technique in pediatric population is limited., Objective: The objective of our study was to retrospectively compare the image quality and radiation dose of pediatric head CT examinations obtained with ASIR compared to pediatric head CT examinations without ASIR in a large patient population., Materials and Methods: Retrospective analysis was performed on 82 pediatric head CT examinations. This group included 33 pediatric head CT examinations obtained with ASIR and 49 pediatric head CT examinations without ASIR. Computed tomography dose index (CTDIvol) was recorded on all examinations. Quantitative analysis consisted of standardized measurement of attenuation and the standard deviation at the bilateral centrum semiovale and cerebellar white matter to evaluate objective noise. Qualitative analysis consisted of independent assessment by two radiologists in a blinded manner of gray-white differentiation, sharpness and overall diagnostic quality., Results: The average CTDIvol value of the ASIR group was 21.8 mGy (SD = 4.0) while the average CTDIvol for the non-ASIR group was 29.7 mGy (SD = 13.8), reflecting a statistically significant reduction in CTDIvol in the ASIR group (P < 0.01). There were statistically significant reductions in CTDI for the 3- to 12-year-old ASIR group as compared to the 3- to 12-year-old non-ASIR group (21.5 mGy vs. 30.0 mGy; P = 0.004) as well as statistically significant reductions in CTDI for the >12-year-old ASIR group as compared to the >12-year-old non-ASIR group (29.7 mGy vs. 49.9 mGy; P = 0.0002). Quantitative analysis revealed no significant difference in the homogeneity of variance in the ASIR group compared to the non-ASIR group. Radiologist assessment of gray-white differentiation, sharpness and overall diagnostic quality in ASIR examinations was not substantially different compared to non-ASIR examinations., Conclusion: The use of ASIR in pediatric head CT examinations allows for a 28% CTDIvol reduction in the 3- to 12-year-old age group and a 48% reduction in the >12-year-old age group without substantially affecting image quality.

Background: Pain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between (1) the amount of surgical pain relief, and (2) the alleles of the gene, on depression and anxiety during the first postoperative year., Results: We collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced >25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood--the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin-2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery., Conclusion: Genomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts.