Multimodal MRI Assessment of Brain Fluid Circulation in Idiopathic Intracranial Hypertension
A Clinical Study Using Multimodal MRI to Evaluate the Effects of Choroid Plexus Function, Glymphatic Function, and Blood-Brain Barrier Function on Cerebrospinal Fluid Circulation in Patients With Idiopathic Intracranial Hypertension
Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by increased pressure inside the skull without an identifiable cause. It can lead to headaches, swelling of the optic nerve, and visual impairment. Alterations in cerebrospinal fluid circulation and fluid exchange within the brain may contribute to this condition, but the underlying mechanisms remain incompletely understood.
This prospective observational study aims to investigate brain fluid circulation in patients with IIH using multimodal magnetic resonance imaging (MRI).A total of 105 participants will be enrolled, including 65 patients with IIH and 40 healthy controls. Healthy controls will be recruited to achieve comparable distributions of age, sex, and body mass index at the group level.
The primary objective is to compare MRI measures related to the choroid plexus, cerebrospinal fluid flow, glymphatic function, cerebral perfusion, and water exchange across the blood-brain barrier between patients with IIH and healthy controls. Secondary objectives are to assess changes in these measures after clinical treatment and examine their associations with intracranial pressure, optic nerve swelling, visual function, and clinical symptoms.
Patients with IIH will undergo clinical, ophthalmological, and MRI assessments at baseline and approximately 3 and 6 months after treatment. Healthy controls will undergo baseline assessments only.
This study will not assign treatments. All clinical management decisions will be made independently by treating physicians. Research MRI examinations will not require contrast agents, and no invasive procedures will be performed solely for research purposes.
Visão geral do estudo
Status
Condições
Descrição detalhada
This is a single-center, prospective observational study designed to characterize brain fluid circulation-related abnormalities in patients with idiopathic intracranial hypertension (IIH) through multimodal MRI and to investigate their clinical relevance and longitudinal changes following routine clinical treatment.
A total of 105 participants will be enrolled, including 65 patients with IIH and 40 healthy controls. Healthy controls will be recruited to achieve comparable distributions of age, sex, and body mass index at the group level. Baseline comparisons will assess differences in imaging markers representing several complementary aspects of brain fluid homeostasis.
Multimodal MRI examinations will include structural T1- and T2-weighted imaging, magnetic resonance venography, phase-contrast MRI, diffusion MRI, resting-state functional MRI, arterial spin labeling, and vascular water exchange imaging (VEXI).
The imaging assessment will include choroid plexus volume, cerebral aqueduct cerebrospinal fluid flow parameters, perivascular space burden, diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, free-water fraction, diffusion tensor imaging-estimated periventricular diffusivity (DTI-EstPVeD), global blood oxygen level-dependent signal-cerebrospinal fluid coupling, cerebral blood flow, and the apparent water exchange rate across the blood-brain barrier (AXR_BBB).
Clinical evaluations in patients with IIH will include cerebrospinal fluid opening pressure, visual acuity, visual field mean deviation, Frisén papilledema grade, retinal nerve fiber layer thickness, and standardized assessments of headache, tinnitus, quality of life, and cognitive function. Trans-stenotic pressure gradients and other invasive clinical measurements will be recorded when available from clinically indicated procedures.
Patients with IIH will undergo repeated clinical, ophthalmological, and multimodal MRI assessments at baseline, 90 ± 14 days, and 180 ± 30 days after clinical treatment. Healthy controls will undergo baseline assessments only. Treatment, including medical management or venous sinus stenting when clinically indicated, will be determined independently by treating physicians and will not be assigned by the study protocol.
The primary analysis will compare baseline imaging measures between patients with IIH and healthy controls, adjusting for age, sex, and body mass index. Longitudinal analyses will evaluate within-patient changes in imaging measures and their associations with changes in intracranial pressure, papilledema, visual function, and clinical symptoms. Comparisons between treatment subgroups will be considered exploratory because treatment allocation is not randomized.
The study aims to provide a comprehensive multimodal imaging characterization of brain fluid circulation-related abnormalities in IIH and to identify potential imaging markers for future disease assessment and treatment monitoring.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: Dapeng Mo, PhD
- Número de telefone: 18811039300
- E-mail: bjttmodp@163.com
Locais de estudo
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Beijing Municipality
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Beijing, Beijing Municipality, China, 100070
- Beijing Tiantan Hospital, Capital Medical University
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Método de amostragem
População do estudo
This single-center prospective observational study will enroll 105 participants, including 65 patients with idiopathic intracranial hypertension (IIH) and 40 healthy controls. Patients with IIH will be recruited at Beijing Tiantan Hospital. Healthy controls will be selected for comparison based on age, sex, and body mass index. Patients with IIH will undergo baseline and follow-up assessments, while healthy controls will undergo baseline assessments only.
Descrição
Inclusion Criteria:
Patients with Idiopathic Intracranial Hypertension (IIH):
Aged 18-60 years.
Clinical manifestations consistent with or highly suggestive of IIH, such as headache, visual disturbance, papilledema, pulsatile tinnitus, or diplopia.
No hydrocephalus, intracranial mass, or other structural cause of increased intracranial pressure on CT or MRI.
Normal cerebrospinal fluid composition.
Lumbar puncture opening pressure ≥250 mmH₂O.
Ability to complete standardized baseline MRI examinations.
Provision of written informed consent.
Healthy Controls:
Aged 18-60 years.
Comparable age, sex, and body mass index to the IIH group.
No history of IIH or symptoms suggestive of increased intracranial pressure.
No papilledema or significant visual or neuro-ophthalmological abnormalities.
No history of major neurological disorders.
Ability to complete standardized multimodal MRI examinations.
Provision of written informed consent.
Exclusion Criteria:
Patients with IIH:
Secondary intracranial hypertension due to cerebral venous sinus thrombosis, intracranial infection, mass lesions, hydrocephalus, or other identifiable causes.
Previous surgical or endovascular procedures substantially affecting intracranial pressure or cerebral venous drainage.
Ophthalmological or neuro-ophthalmological disorders that may interfere with visual assessment.
Recent head trauma or intracranial surgery, major brain abnormalities, or neurological disorders that may substantially affect MRI assessments; long-term use of medications considered likely to interfere with intracranial pressure or fluid metabolism.
Pregnancy or breastfeeding.
Severe systemic illness or MRI contraindications.
Inadequate baseline MRI quality or substantial missing clinical data preventing reliable analysis.
Any other condition considered unsuitable for participation by the investigator.
Healthy Controls:
History of IIH, cerebral venous disorders, intracranial mass lesions, hydrocephalus, or other neurological conditions potentially affecting brain fluid dynamics.
Ophthalmological or neuro-ophthalmological disorders that may interfere with visual assessment.
Pregnancy or breastfeeding.
MRI contraindications.
Severe systemic illness preventing completion of study examinations.
Any other condition considered unsuitable for participation by the investigator.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Modelos de observação: CASE_CONTROL
- Perspectivas de Tempo: PROSPECTIVE
Coortes e Intervenções
Grupo / Coorte |
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IIH Patients
Sixty-five patients with idiopathic intracranial hypertension (IIH) will undergo baseline clinical, ophthalmological, and multimodal MRI assessments. Follow-up assessments will be performed at 90 ± 14 days and 180 ± 30 days after clinical treatment. Treatment, including medical management or venous sinus stenting when clinically indicated, will be determined independently by treating physicians and will not be assigned by the study protocol. |
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Healthy Controls
Forty healthy controls will be recruited to achieve comparable distributions of age, sex, and body mass index to those of the IIH group at the group level. Healthy controls will undergo baseline demographic assessment, noninvasive screening, and multimodal MRI only. No longitudinal follow-up or study-related invasive procedures will be performed in healthy controls. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Total Choroid Plexus Volume
Prazo: Baseline
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Total bilateral choroid plexus volume (mm³) measured using structural MRI. |
Baseline
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Whole-Brain-Normalized Choroid Plexus Volume
Prazo: Baseline
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Choroid plexus volume normalized to whole-brain volume, expressed as a dimensionless ratio. |
Baseline
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Peak Systolic Cerebrospinal Fluid Velocity in the Cerebral Aqueduct
Prazo: Baseline
|
Peak systolic cerebrospinal fluid velocity (cm/s) in the cerebral aqueduct measured using phase-contrast MRI. |
Baseline
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Peak Diastolic Cerebrospinal Fluid Velocity in the Cerebral Aqueduct
Prazo: Baseline
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Peak diastolic cerebrospinal fluid velocity (cm/s) in the cerebral aqueduct measured using phase-contrast MRI. |
Baseline
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Mean Cerebrospinal Fluid Velocity in the Cerebral Aqueduct
Prazo: Baseline
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Mean cerebrospinal fluid velocity (cm/s) in the cerebral aqueduct measured using phase-contrast MRI. |
Baseline
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Net Cerebrospinal Fluid Flow Rate Through the Cerebral Aqueduct
Prazo: Baseline
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Net cerebrospinal fluid flow rate (mL/min) through the cerebral aqueduct measured using cardiac-gated phase-contrast MRI. |
Baseline
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Total Perivascular Space Volume Fraction
Prazo: Baseline
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Ratio of MRI-visible perivascular space volume to intracranial volume, derived from structural MRI. |
Baseline
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Overall Diffusion Tensor Imaging Along the Perivascular Space Index
Prazo: Baseline
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Overall diffusion tensor imaging along the perivascular space (DTI-ALPS) index derived from diffusion MRI, expressed as a dimensionless ratio. |
Baseline
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White Matter Free-Water Fraction
Prazo: Baseline
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Extracellular free-water fraction in cerebral white matter estimated using diffusion MRI. |
Baseline
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Diffusion Tensor Imaging-Estimated Periventricular Diffusivity Index
Prazo: Baseline
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Periventricular diffusivity (PVeD) index estimated from the transverse tensor ratio (TTR) in periventricular white matter using diffusion tensor MRI. |
Baseline
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Global Blood Oxygen Level-Dependent Signal-Cerebrospinal Fluid Coupling
Prazo: Baseline
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Pearson correlation coefficient (r) between the global gray-matter BOLD signal and the CSF inflow signal derived from resting-state functional MRI. |
Baseline
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Whole-Brain Cerebral Blood Flow
Prazo: Baseline
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Mean whole-brain cerebral blood flow (mL/100 g/min) measured using arterial spin labeling MRI. |
Baseline
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Gray Matter Cerebral Blood Flow
Prazo: Baseline
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Mean cerebral blood flow (mL/100 g/min) in gray matter measured using arterial spin labeling MRI. |
Baseline
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White Matter Cerebral Blood Flow
Prazo: Baseline
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Mean cerebral blood flow (mL/100 g/min) in white matter measured using arterial spin labeling MRI. |
Baseline
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White Matter Apparent Blood-Brain Barrier Water Exchange Rate
Prazo: Baseline
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Apparent blood-brain barrier water exchange rate (AXR_BBB) in cerebral white matter estimated using vascular water exchange imaging (VEXI). |
Baseline
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Deep Gray Matter Apparent Blood-Brain Barrier Water Exchange Rate
Prazo: Baseline
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Apparent blood-brain barrier water exchange rate (AXR_BBB) in deep gray matter estimated using vascular water exchange imaging (VEXI). |
Baseline
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Cerebrospinal Fluid Opening Pressure
Prazo: Baseline
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Cerebrospinal fluid opening pressure (mmH₂O) measured during clinically indicated lumbar puncture in patients with IIH. |
Baseline
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Trans-Stenotic Venous Pressure Gradient
Prazo: Baseline
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Pressure gradient (mmHg) across venous sinus stenosis measured during clinically indicated venous manometry in patients with IIH. |
Baseline
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Visual Acuity
Prazo: Baseline
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Visual acuity recorded as a numerical measure during ophthalmological examination in patients with IIH. |
Baseline
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Visual Field Mean Deviation
Prazo: Baseline
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Visual field mean deviation (dB) measured using automated perimetry in patients with IIH. |
Baseline
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Frisén Papilledema Grade
Prazo: Baseline
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Papilledema severity assessed using the Frisén grading scale (0-5), with higher grades indicating greater severity. |
Baseline
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Retinal Nerve Fiber Layer Thickness
Prazo: Baseline
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Retinal nerve fiber layer thickness (µm) measured using optical coherence tomography. |
Baseline
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Headache Impact Test-6 Score
Prazo: Baseline
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Total score on the six-item Headache Impact Test (HIT-6), ranging from 36 to 78, with higher scores indicating greater headache-related impact. |
Baseline
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Tinnitus Handicap Inventory Score
Prazo: Baseline
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Total score on the Tinnitus Handicap Inventory (THI), ranging from 0 to 100, with higher scores indicating greater tinnitus-related handicap. |
Baseline
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EuroQol 5-Dimension Index Score
Prazo: Baseline
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Health-related quality of life measured using the EQ-5D index value, with higher scores indicating better health status. |
Baseline
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Mini-Mental State Examination Score
Prazo: Baseline
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Total score on the Mini-Mental State Examination (MMSE), ranging from 0 to 30, with higher scores indicating better cognitive performance. |
Baseline
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Montreal Cognitive Assessment Score
Prazo: Baseline
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Total score on the Montreal Cognitive Assessment (MoCA), ranging from 0 to 30, with higher scores indicating better cognitive performance. |
Baseline
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Oral Symbol Digit Modalities Test Score
Prazo: Baseline
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Number of correct responses on the Oral Symbol Digit Modalities Test (Oral SDMT), with higher scores indicating better information processing speed. |
Baseline
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Trail Making Test Part A Completion Time
Prazo: Baseline
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Completion time (seconds) for the Trail Making Test Part A (TMT-A), with longer times indicating slower performance. |
Baseline
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Trail Making Test Part B Completion Time
Prazo: Baseline
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Completion time (seconds) for the Trail Making Test Part B (TMT-B), with longer times indicating slower performance. |
Baseline
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Stroop Color-Word Interference Completion Time
Prazo: Baseline
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Completion time (seconds) for the interference condition of the Stroop Color-Word Test, with longer times indicating poorer performance. |
Baseline
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Backward Digit Span Score
Prazo: Baseline
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Number of digit sequences correctly recalled in reverse order, with higher scores indicating better working memory performance. |
Baseline
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change From Baseline in Whole-Brain-Normalized Choroid Plexus Volume
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in choroid plexus volume normalized to whole-brain volume, measured using structural MRI. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change From Baseline in Net Cerebrospinal Fluid Flow Rate Through the Cerebral Aqueduct
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in net cerebrospinal fluid flow rate (mL/min) through the cerebral aqueduct measured using phase-contrast MRI. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change From Baseline in Total Perivascular Space Volume Fraction
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in the ratio of MRI-visible perivascular space volume to intracranial volume. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change From Baseline in Overall DTI-ALPS Index
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in the overall DTI-ALPS index derived from diffusion MRI. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change From Baseline in White Matter Free-Water Fraction
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in white matter extracellular free-water fraction estimated using diffusion MRI. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change From Baseline in Global BOLD-CSF Coupling
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
|
Change from baseline in the Pearson correlation coefficient between the global gray-matter BOLD signal and the CSF inflow signal. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
|
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Change From Baseline in Whole-Brain Cerebral Blood Flow
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in mean whole-brain cerebral blood flow (mL/100 g/min) measured using arterial spin labeling MRI. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
|
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Change From Baseline in White Matter Apparent Blood-Brain Barrier Water Exchange Rate
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in apparent blood-brain barrier water exchange rate in white matter estimated using VEXI. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change From Baseline in Frisén Papilledema Grade
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in papilledema severity assessed using the Frisén grading scale (0-5). |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change From Baseline in Visual Field Mean Deviation
Prazo: Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
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Change from baseline in visual field mean deviation (dB) measured using automated perimetry. |
Baseline, 90 ± 14 days and 180 ± 30 days after clinical treatment (IIH patients only)
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Dapeng Mo, PhD, Beijing Tiantan Hospital
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
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Outros números de identificação do estudo
- HX-B-2026054
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
There is currently no plan to share individual participant data outside the study team.
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