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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.
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Doença de Huntington , Adulto , Humanos , Doença de Huntington/diagnóstico por imagem , Doença de Huntington/líquido cefalorraquidiano , Ventrículos Cerebrais , Aqueduto do Mesencéfalo , Imageamento por Ressonância Magnética/métodos , Crânio , Líquido CefalorraquidianoRESUMO
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.
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Medula Cervical , Humanos , Medula Cervical/diagnóstico por imagem , Reprodutibilidade dos Testes , Imagem de Difusão por Ressonância Magnética/métodos , Medula Espinal/diagnóstico por imagem , Razão Sinal-Ruído , AlgoritmosRESUMO
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.
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Medula Cervical , Esclerose Múltipla , Humanos , Medula Cervical/diagnóstico por imagem , Medula Cervical/patologia , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Estudos Retrospectivos , Projetos Piloto , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
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.
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Sistema Glinfático , Doenças do Sistema Nervoso , Encéfalo/diagnóstico por imagem , Sistema Glinfático/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
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.
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Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Biópsia Guiada por Imagem/métodos , Posicionamento do Paciente/métodos , Segurança do Paciente , Tomografia Computadorizada por Raios X/métodos , Humanos , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
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.
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Angiofibroma/diagnóstico por imagem , Cavidade Nasal/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Nasofaringe/anatomia & histologia , Órbita/diagnóstico por imagem , Osso Esfenoide/anatomia & histologia , Adolescente , Criança , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
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.
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Encéfalo/diagnóstico por imagem , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pediatria/métodos , Estudos RetrospectivosRESUMO
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 T1-weighted, 3D T2-weighted, and 2D T2-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 T1-weighted MRI, Dice coefficient = 0.72, Hausdorff distance = 2.22 mm, AUC = 0.87 for T2-weighted MRI, and Dice coefficient = 0.74, Hausdorff distance = 1.69 mm, AUC = 0.87 for T2-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 T1-weighted and T2-weighted FLAIR, T1-weighted and T2-weighted, and T2-weighted and T2-weighted FLAIR models, respectively. Mean lateral ventricle choroid plexus volume across all participants was 3.20 ± 1.4 cm3; a significant, positive relationship (R2 = 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_seg ).
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Aprendizado Profundo , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Processamento de Imagem Assistida por Computador/métodos , Longevidade , Plexo Corióideo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
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.
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Transtornos Cerebrovasculares , Hiperemia , Doença de Moyamoya , Humanos , Plexo Corióideo/diagnóstico por imagem , Constrição Patológica , Doença de Moyamoya/diagnóstico por imagem , IsquemiaRESUMO
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.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Encéfalo/patologia , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Veias/patologiaRESUMO
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.
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Medula Cervical , Imageamento por Ressonância Magnética , Esclerose Múltipla , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Adulto , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Medula Cervical/diagnóstico por imagem , Medula Cervical/patologia , Pessoa de Meia-Idade , Vértebras Cervicais/diagnóstico por imagem , Adulto Jovem , Estudos de Casos e Controles , Valores de ReferênciaRESUMO
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/mm2) 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 mm2/s) relative to Parkinson's disease (D = 0.00517 ± 0.00110 mm2/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.
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Líquido Cefalorraquidiano , Imagem de Difusão por Ressonância Magnética , Doença de Parkinson , Humanos , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Líquido Cefalorraquidiano/diagnóstico por imagem , Líquido Cefalorraquidiano/fisiologia , Movimento (Física)RESUMO
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 T2-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 T2-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 cm3 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 mm3 per year (p < 0.001) for total AG volume and 0.54 mm3 (p < 0.001) for maximum AG volume. CONCLUSIONS: A tool that can be applied to quantify PSD and AG volumes from commonly acquired T2-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 ).
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Aprendizado Profundo , Longevidade , Adulto , Humanos , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Imageamento por Ressonância Magnética/métodos , Redes Neurais de Computação , Espectroscopia de Ressonância Magnética , Processamento de Imagem Assistida por Computador/métodosRESUMO
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 T1-weighted, T2-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 cm3) 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.
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Plexo Corióideo , Longevidade , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Plexo Corióideo/diagnóstico por imagem , Plexo Corióideo/metabolismo , Ventrículos Cerebrais , Encéfalo , Perfusão , Líquido Cefalorraquidiano/fisiologiaRESUMO
Background: The choroid plexus functions as the blood-cerebrospinal fluid barrier, plays an important role in neurofluid production and circulation, and has gained increased attention in light of the recent elucidation of neurofluid 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 3-D T1-weighted, 3-D T2-weighted, and 2-D T2-weighted FLAIR MRI and gold-standard manual segmentations in healthy 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 healthy adults (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 T1-weighted MRI, Dice coefficient=0.72, Hausdorff distance=2.22 mm, AUC=0.87 for T2-weighted MRI, and Dice coefficient=0.74, Hausdorff distance=1.69 mm, AUC=0.87 for T2-weighted FLAIR MRI; values did not differ significantly between2 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 T1-weighted and T2-FLAIR, T1-weighted and T2-weighted, and T2-weighted and T2-FLAIR models, respectively. Mean lateral ventricle choroid plexus volume across all participants was 3.20±1.4 cm3; a significant, positive relationship (R2=0.54; slope=0.047) 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_seg).
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BACKGROUND: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation and accumulation of a-synuclein protofibrils. New diagnostic methods assess a-synuclein aggregation characteristics from cerebrospinal fluid and recent pathophysiologic mechanisms suggest that cerebrospinal fluid circulation disruptions may precipitate a-synuclein retention. Here, we test the hypothesis that cerebrospinal fluid motion at the level of the suprasellar cistern is reduced in Parkinson's disease relative to healthy participants and this reduction relates to choroid plexus perfusion. METHODS: Diffusion weighted imaging (spatial resolution=1.8×1.8×4 mm) magnetic resonance imaging with cycling of diffusion weightings (b-values=0, 50, 100, 200, 300, 700, and 1000 s/mm2) over the approximate kinetic range of suprasellar cistern neurofluid motion was applied at 3-Tesla in Parkinson's disease (n=27; age=66±6.7 years) and healthy (n=32; age=68±8.9 years) participants. Wilcoxon rank-sum tests were applied to test the primary hypothesis that the decay rate of cerebrospinal fluid signal as a function of b-value, which reflects increasing fluid motion, is reduced in persons with versus without Parkinson's disease and inversely relates to choroid plexus activity assessed from perfusion-weighted magnetic resonance imaging (Spearman rank-order correlation; significance-criteria: p<0.05). RESULTS: Consistent with the primary hypothesis, decay rates were higher in healthy (D=0.00328±0.00123mm2/s) relative to Parkinson's disease (D=0.00256±0.0094mm2/s) participants (p=0.016). This finding was preserved after controlling for age and sex. An inverse correlation between choroid plexus perfusion and decay rate (p=0.011) was observed in Parkinson's disease participants. CONCLUSIONS: Cerebrospinal fluid motion at the level of the suprasellar cistern is often reduced in adults with versus without Parkinson's disease and this reduction correlates on average with choroid plexus perfusion.
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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.
Assuntos
Substância Cinzenta , Medula Espinal , Animais , Humanos , Medula Espinal/diagnóstico por imagem , Medula Espinal/fisiologia , Substância Cinzenta/diagnóstico por imagem , Corno Dorsal da Medula Espinal , Córtex Cerebral , Imageamento por Ressonância Magnética/métodos , Voluntários Saudáveis , Encéfalo , Mapeamento Encefálico/métodosRESUMO
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 B1, B0, and R1 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.
RESUMO
One of the pathological hallmarks of Alzheimer's and related diseases is the increased accumulation of protein amyloid-ß 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-ß accumulation in older adults. Participants (N = 23) were scanned at 3.0â T with 3D T2-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-ß tracer 11C-Pittsburgh Compound B to quantify global cerebral amyloid-ß accumulation. Spearman's correlation analyses revealed a significant relationship between global amyloid-ß 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-ß 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-ß accumulation. These findings are discussed in the context of our growing understanding of the physiological mechanisms of amyloid-ß aggregation and clearance via neurofluids.
RESUMO
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 T1-weighted and T2-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.