Clinical Study of Structural and Functional Evaluation of the Visual Pathway

• ClinicalTrials.gov Identifier: NCT03591315
• Recruitment Status: Unknown
• First Posted: July 19, 2018
• Last Update Posted: July 23, 2018
• Sponsor: Xiangya Hospital of Central South University
• Information provided by (Responsible Party): Xiangya Hospital of Central South University

Study Description

Brief Summary:

Sellar area tumors such as pituitary adenoma, craniopharyngioma and meningioma, etc, commonly lead to visual impairment symptoms. Patients suffer from a loss of visual acuity (VA) and visual field defects (VF) due to a local compression on the optic chiasma by the tumor. In the management of these patients, it is an important goal to evaluate their visual function throughout the treatment, so as to predict the outcome of the visual function .

Since the visual pathway contains a huge complex network of both structure and function, traditional simplex evaluation of VA and VF is obviously not enough. Former studies have revealed changes in the visual network and cortex structure in neurodegenerative diseases and optic neuritis, yet the functional and structural changes caused by local tumor compression and their relation to the visual cortex activity patterns needs further research.

The objective of this research is to asses the visual function in patients with sellar area tumor 1 week preoperatively (baseline),72 hours postoperatively(checking point 1) and at 3 months follow up(checkpoint 2). By using multimodal evaluation including visual resting and task state fMRI, diffusion tensor imaging (DTI), etc. The investigators aim to reveal the changes in functional connectivity (FC), amplitude of low frequency fluctuation (ALFF), regional homogeneity (REHO) ,visual cortex activity patterns and tract-based spatial statistics (TBSS).

Condition or disease	Intervention/treatment
Pituitary Adenoma; Visual Impairment; Sellar Tumor; Neuroimaging	Diagnostic Test: resting state fMRI; Diagnostic Test: visual tasking state fMRI; Diagnostic Test: diffusion tensor imaging; Diagnostic Test: automated visual field; Diagnostic Test: visual acuity

Detailed Description:

Detailed Description:

Study objective

Visual pathway contains both structural and functional network. When it is impacted by neurodegenerative diseases, neuritis or direct mechanical pressure, visual impairment occurs due to damage to the pathway. Former study on Parkinson's disease (Dagmar H. Heep et al, Radiology, 2017 ) found loss of functional connectivity in posterior and paracentral brain regions, while a study on optic neuritis (Yael Backner et al, JAMA Neurology,2018) showed an increase in functional connectivity and slightly loss in optic fiber integrity. Instead of simplex resting-state fMRI，the investigators of this study aim to assess:

1. whether similar changes in functional networking occur when visual pathway is impacted by chiasma compression from tumors in sellar area (by resting-state fMRI).
2. The correlation between local chiasma compression and visual cortex activation pattern ( by visual tasking-state fMRI).
3. Changes and recovery of the white matter fiber structure in the visual pathway.

( by diffusion tensor imaging, DTI).

Method Participants: 60 adult participants (18-60 years old ) will be enrolled in the department of Neurosurgery at Xiangya Hospital of Central South University. The experimental arm will consist of 30 patients with visual impairment symptoms caused by chiasma compression by sellar area tumors (Tumor Group, TG). The control arm will consist of 30 healthy controls without any nervous system disease or visual impairment (Healthy Control Group, HC, control arm).

Study design: Transversal and Longitudinal, single center, comparative study is designed to evaluate functional and structural visual networking of sellar area tumor patients and healthy controls. The study involves assessment with resting-state fMRI, tasking-state fMRI and DTI. Patients of experimental arm will be evaluated by multimodal fMRI at 3 different checkpoints (baseline is 1 week preoperative ,checkpoint 1 is 72 hours postoperative ,checkpoint 2 is 3 months follow up ). Participants of control arm will be evaluated only once. Transversal comparison will be conducted between preoperative tumor patients and healthy controls, while longitudinal comparison will be within tumor group at baseline and two other different checkpoints.

MRI data acquisition and analysis strategy: In this study, the MRI data is acquired by Siemens 3.0T Prisma scanner, including sequences of mprage T1 , diffusion tensor imaging, resting-state fMRI and visual stimulation task fMRI. Resting-state fMRI longitudinal data analysis includes functional connectivity (FC), amplitude of low frequency fluctuation (ALFF) and regional homogeneity (REHO) to assess visual functional networking in both group. These Data wil be analysed using a multivariate approach and independent component analysis (ICA). Visual tasking fMRI will be conducted under classic black and white "chess board" simulation on each eye. For the evaluation of structural visual network, afferent visual pathway (optic tract and radiation ), fiber tracking as well as tract-based spatial statistics (TBSS) will be analyzed within both arms at baseline,checkpoint 1 and checkpoint 2 of the experimental arm will verify changing and recovering process of the visual pathway after chiasma decompression.

Primary outcomes

1. The difference in visual pathway anatomy and functional network between preoperative sellar area tumor patients and healthy controls. Tumor patients will be evaluated clinically by visual acuity (VA), visual field (VF), tumor height and chiasma thickness.
2. The verification of the correlation between patterns of chiasma compression and visual cortex activity. Revealing the difference of visual cortex activity patterns between both arms.

Secondary outcomes Throughout the 3 months follow up of the experimental arm patients, observe and verify the recovery process of both functional and structural visual network after chiasma decompression and evaluate its correlation with clinical visual function outcome.

Statistics

1. An analysis of two sample T test between the two groups will be performed to assess the difference of FC,REHO,ALFF and visual cortex activity pattern between resting state data and data from the visual task of TG and HC.
2. An analysis of variance (ANOVA) within TG group will be performed to assess the changes and recovery of FC, REHO, ALFF and visual cortex activity pattern via resting state data and data from the visual task's data.

Correlations will be explored between multimodal fMRI parameters (both functional and structural) and clinical criteria (e.g VA,VF, tumor size, visual outcome, etc).

Study Design

• Study Type: Observational
• Estimated Enrollment: 60 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Multimodal Evaluation on Visual Pathway Predicts the Surgical Curative Effects in Sellar Area Tumors
• Estimated Study Start Date: July 2018
• Estimated Primary Completion Date: December 2018
• Estimated Study Completion Date: January 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
TG group; Patients with visual impairment caused by chiasma compression from sellar area tumors will undergo the following examinations: resting state fMRI, visual tasking state fMRI, diffusion tensor imaging (DTI), visual acuity and automated visual field test.	Diagnostic Test: resting state fMRI; Define the visual resting state network.; Other Name: V-RS; Diagnostic Test: visual tasking state fMRI; Using visual task stimulation to identify the activation characteristic of primary visual cortex.; Diagnostic Test: diffusion tensor imaging; Define the integrity of white matter fibers in the visual pathway.; Other Name: DTI; Diagnostic Test: automated visual field; Identify the existence and type of visual field defect.; Other Name: VF; Diagnostic Test: visual acuity; Assess the visual acuity by using ETDRS scales.; Other Name: VA
HC group; Volunteers with no visual impairment(visual acuity of both eyes >1.0) or Nervous System disease will undergo the following examinations: resting state fMRI, visual tasking state fMRI, diffusion tensor imaging (DTI), visual acuity and automated visual field test.	Diagnostic Test: resting state fMRI; Define the visual resting state network.; Other Name: V-RS; Diagnostic Test: visual tasking state fMRI; Using visual task stimulation to identify the activation characteristic of primary visual cortex.; Diagnostic Test: diffusion tensor imaging; Define the integrity of white matter fibers in the visual pathway.; Other Name: DTI; Diagnostic Test: automated visual field; Identify the existence and type of visual field defect.; Other Name: VF; Diagnostic Test: visual acuity; Assess the visual acuity by using ETDRS scales.; Other Name: VA

Outcome Measures

Primary Outcome Measures :

1. Change on functional connectivity of visual resting network [ Time Frame: Change from baseline (1 week preoperative) functional connectivity of visual resting network at 3 days postoperative and 3 moths postoperative. ]
   Outcomes of visual resting state fMRI to assess the functional connectivity (FC) of visual resting network.
2. Change on signal strength of the visual cortex activation by visual tasking state fMRI (visual BOLD fMRI). [ Time Frame: Change from baseline (1 week preoperative) visual cortex activation signal strength at 3 days postoperative and 3 moths postoperative. ]
   Outcomes of visual BOLD fMRI to assess the function of visual cortex by measuring the signal strength (T-test score) of the visual cortex activation.
3. Change on anatomical Connectivity of the posterior visual pathway [ Time Frame: Change from baseline (1 week preoperative) TBSS result at 3 days postoperative and 3 moths postoperative. ]
   Outcomes of tract-based spatial statistics (TBSS) to assess the integrity of the white matter fibers in the posterior visual pathway.

Secondary Outcome Measures :

1. Change on visual acuity [ Time Frame: Change from baseline (1 week preoperative) visual acuity at 3 days postoperative and 3 moths postoperative. ]
   Outcomes of visual acuity test for evaluation of the visual function impairment and recovery.
2. Change on visual field. [ Time Frame: Change from baseline (1 week preoperative) visual field at 3 days postoperative and 3 moths postoperative. ]
   Visual Field Defects via Humphrey visual field chart, Mean Deviation and Standard Deviation in the patients' group at different checkpoints.
3. Change on amplitude of low frequency fluctuation (ALFF) of visual resting network [ Time Frame: Change from baseline (1 week preoperative) ALFF of visual resting network at 3 days postoperative and 3 moths postoperative. ]
   Visual resting state fMRI data will be analysed to assess the ALFF data of visual resting network
4. Change on regional homogeneity (REHO) of visual resting network [ Time Frame: Change from baseline (1 week preoperative) REHO of visual resting network at 3 days postoperative and 3 moths postoperative. ]
   Outcomes of visual resting state fMRI to assess the regional homogeneity (REHO) of visual resting network.
5. Change on fractional atrophy (FA) value of the posterior visual pathway. [ Time Frame: Change from baseline (1 week preoperative) FA of the posterior visual pathway at 3 days postoperative and 3 moths postoperative.. ]
   Outcomes of fractional atrophy (FA) on the posterior visual pathway via diffusion tensor imaging (DTI) and fiber tractography.
6. Change on axial diffusivity (AD) of the posterior visual pathway. [ Time Frame: Change from baseline (1 week preoperative) AD value of the posterior visual pathway at 3 days postoperative and 3 moths postoperative.. ]
   Outcomes of axial diffusivity (AD) value on the posterior visual pathway via diffusion tensor imaging (DTI) and fiber tractography.
7. Change on radial diffusivity (RD) of the posterior visual pathway. [ Time Frame: Change from baseline (1 week preoperative) RD value of the posterior visual pathway at 3 days postoperative and 3 moths postoperative.. ]
   Outcomes of radial diffusivity (RD) value on the posterior visual pathway via diffusion tensor imaging (DTI) and fiber tractography.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Admitted sellar area tumor patients in the Neurosurgery Department at Xiangya Hospital of Central South University.

Criteria

Inclusion Criteria:

1. patients with sellar area tumors ( including pituitary adenoma,craniopharyngioma and meningioma) resulting a visual deficit (loss of visual acuity or visual field).
2. Male or female between 18y to 60y.
3. Patients treated with transsphenoidal surgery.
4. Patients agreeing to participate in the study and willing to sign an informed consent.

Exclusion Criteria:

1. tumor height ≥ 4cm.
2. Patients with recurrent tumors, previous craniotomy or gamma knife treatment
3. Visual impairment caused by other diseases.
4. Mental disorders, inability to cooperate with treatment and follow up visits.
5. Patients with other serious complications.

Contacts and Locations

Contacts

Contact: Liu Z Xiong, MD/PhD; 13607318785; zhixiongliu@csu.edu.cn

Contact: Zhong W Ming, MD; 18874002961; sjwkkarl@163.com

Locations

China, Hunan

Xiangya Hospital of Central South University

Changsha, Hunan, China, 410001

Contact: Liu Z Xiong, MD/PhD 13607318785 zhixiongliu@csu.edu.cn

Sponsors and Collaborators

Xiangya Hospital of Central South University

Investigators

• Study Chair: Liu Z Xiong, MD/PhD; Neurosurgery department, Xiangya Hospital of Central South University, Changsha, Hunan, China

More Information

Publications of Results:

Backner Y, Kuchling J, Massarwa S, Oberwahrenbrock T, Finke C, Bellmann-Strobl J, Ruprecht K, Brandt AU, Zimmermann H, Raz N, Paul F, Levin N. Anatomical Wiring and Functional Networking Changes in the Visual System Following Optic Neuritis. JAMA Neurol. 2018 Mar 1;75(3):287-295. doi: 10.1001/jamaneurol.2017.3880.

Hepp DH, Foncke EMJ, Olde Dubbelink KTE, van de Berg WDJ, Berendse HW, Schoonheim MM. Loss of Functional Connectivity in Patients with Parkinson Disease and Visual Hallucinations. Radiology. 2017 Dec;285(3):896-903. doi: 10.1148/radiol.2017170438. Epub 2017 Sep 27.

• Responsible Party: Xiangya Hospital of Central South University
• ClinicalTrials.gov Identifier: NCT03591315
• Other Study ID Numbers: 201611627
• First Posted: July 19, 2018
• Last Update Posted: July 23, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xiangya Hospital of Central South University:

visual pathway; functional magnetic resonance imaging; pituitary adenoma

Additional relevant MeSH terms:

Adenoma; Pituitary Neoplasms; Pituitary Diseases; Vision Disorders; Vision, Low; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms