GlioblastomaNVUCVRNCT06797661
Insights Into the Pathophysiology of Neurovascular Uncoupling in Patients With Brain Lesions.
A study testing Functional MRI, FDG-PET and Structural MRI in people with Glioblastoma and Glioma, run by Erasme University Hospital at 1 site in Belgium.
Trial summary
Neurovascular uncoupling (NVU) represents a major source of potential bias for the identification of eloquent brain regions through activation procedures in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Glioblastoma, Glioma, Astrocytoma
- What is being tested?
- Functional MRI, FDG-PET and Structural MRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteBelgium
- Study dates
- 17 Feb 2025to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients in the study include prior imaging showing a potentially resectable intra-cerebral mass lesion. Patient has to be included before surgery, chemotherapy and radiation
Who cannot join
- previous brain surgery
- respiratory failure
- Asthma
- Claustrophobia
- Previous adverse reaction to gadovist (contrast agent)
- Pregnancy and Breath feeding
- Diabetes (type I and II)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
HUB-Erasme Hospital
Brussels, 1060
Thibault Vanbutsele, 25558167 ext. +32, thibault.vanbutsele@hubruxelles.be
About this study
Neurovascular uncoupling (NVU) represents a major source of potential bias for the identification of eloquent brain regions through activation procedures in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI).
Same region shows proper pattern in glucose metabolism in victiny of brain lesions, investigated with positron emitted tomography with radiolabeled glucose (PET-FDG) This research project aims at investigating the mechanisms of NVU by using a multimodal noninvasive imaging approach in neurosurgical patients.
Read the detailed description
Brain metabolism and blood flow are tightly coupled with neuronal activity. Changes in neuronal activity result in the modulation of glucose consumption by neurons. Both glucose and lactate levels return to their baseline instantly as neuronal activity ceases, a phenomenon known as neurometabolic coupling. Given the limited energetic reserves in the central nervous system, neuronal activity heavily relies on the finely regulated supply of glucose from the bloodstream. However, the dynamic increase in cerebral blood flow (CBF) during neuronal activation far exceeds the increase in oxidative metabolism. This relative hyperemic response ensures an increased oxygen gradient between blood vessels and tissue, providing ample oxygen supply. The close temporal and regional link between changes in neuronal activity and CBF increase is referred to as neurovascular coupling (NVC) and involves a complex cascade of events. Neurotransmitters, such as glutamate, released at synapses bind to receptors on neurons and astrocytes, leading to the release of various chemical mediators, like nitric oxide and prostaglandins, which directly act on arterial smooth muscle tone. More complex and incompletely understood signaling pathways, including Na+ and Ca2+-mediated astrocyte signaling mechanisms, are also presumed to contribute to NVC.
The tight relationship between neuronal activity and both regional blood flow and metabolism has provided the basis for non-invasive functional brain imaging methods, including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). PET using [18Fluor ]-fluorodeoxyglucose (FDG) is a technique based on the accumulation of metabolized FDG (i.e., FDG-6-phosphate) in the astrocyte-neuron complex, reflecting the level of glucose consumption. Since the seminal works of Sokoloff et al., glucose utilization is considered a valid, accurate, and quantitative indicator of the level of local neuronal activity within the brain. In contrast, fMRI, which relies on the blood oxygen level-dependent (BOLD) signal, provides indirect information about neuronal activity by investigating perfusion-related changes coupled with neuronal activity. In areas of increased CBF due to modulations in neuronal activity, oxygen delivery exceeds the rate of oxygen utilization, inducing a local increase in the oxy-/deoxy-hemoglobin ratio. This leads to a detectable increase in the magnetic-susceptibility weighted MRI signal.
One of the earliest and still recognized clinical applications of fMRI has been preoperative functional mapping of the primary sensorimotor cortex in patients with brain tumors. This technique has significantly impacted surgical planning, often enabling more aggressive approaches than those considered without functional localization. fMRI has also been increasingly used in the presurgical evaluation of patients with vascular or epileptogenic lesions. However, despite the growing use of BOLD fMRI in patients with brain lesions, this technique has major limitations that must be considered when interpreting fMRI results in such populations. The main limitation is the impairment of BOLD signal changes due to lesion-related loss of normal vascular coupling with neuronal activity, a phenomenon referred to as neurovascular uncoupling (NVU). This can result in false-negative or false-positive results in critical eloquent cortex. If neuronal activity is preserved in diseased but viable cortex, NVU is presumed to occur due to astrocytic, neurotransmitter, or vascular dysfunction.
NVU has been mainly reported in patients with high-grade glial tumors and meningiomas. In such patients, the volume of task-based fMRI signal increases has been shown to be reduced adjacent to the tumor compared to homologous fMRI signal changes in the contralesional hemisphere, despite the absence of neurological deficit. In line with experimental data in healthy subjects showing that BOLD signal may decrease as cerebral blood volume (CBV) increases, impaired cerebrovascular reactivity (CVR) in brain tumor patients may be explained by changes in local perfusion. In hypervascularized tumors such as high-grade gliomas and meningiomas, local hyperperfusion has been suggested to explain the decreased BOLD signal on task-based fMRI. However, recent studies have demonstrated that NVU may also occur in low-grade gliomas. Given the absence of hyperperfusion in this tumor type, different mechanisms need to be considered. In low-grade gliomas, the observed NVU is currently thought to be, at least in part, due to disruption of astrocyte-vascular coupling (gliovascular uncoupling). Patients with arteriovenous malformations may exhibit impaired peri-nidal cerebrovascular reserve due to high-flow shunting, making perfusion-dependent mapping signals unreliable. Epilepsy patients may also exhibit regional impairment of CVR due to dramatic increases in brain metabolism and CBF during the ictal period, disruption of the brain-blood barrier, and an acute loss of cerebral pressure autoregulation.
According to previous research, CVR can be studied through the "hypercapnia challenge" during fMRI recordings, including breath-hold fMRI (BH fMRI) and carbogen inhalation fMRI. Hypercapnia is a potent vasodilator that increases the BOLD baseline signal by detecting an increase in tissue oxygenation resulting from increases in CBF while oxidative metabolism demands are considered to remain constant. However, the influence of hypercapnia on neural activity and neurometabolic/neurovascular couplings is not well understood and remains debated. In practice, areas of reduced or absent hypercapnia-induced increase in fMRI signal on CVR maps compared to homologous contralateral activation are assumed to indicate NVU. Recent studies suggest potential advantages in using resting-state (rs) fMRI as a preoperative technique. rs-fMRI is a functional neuroimaging technique that allows the measurement of spontaneous brain activity in patients at rest. Spontaneous BOLD signal fluctuations are highly correlated in distinct and long-ranged brain regions, indicating functional connectivity within specific and highly organized neuroanatomical networks. Functional connectivity studies have also demonstrated a high degree of spatial correlation between rs-fMRI functional brain connectivity and those studied during a hypercapnia challenge. Interestingly, recent research suggests that rs-BOLD signal may be impaired in patients in whom task-based increases in fMRI signals are reduced or absent due to NVU. Therefore, alterations in functional brain connectivity studied with rs-fMRI might provide insights into the presence of NVU as studied with CVR during hypercapnia. Such findings would be of interest in clinical practice as they could avoid the need for CVR-mapping with a hypercapnia challenge.
- Conditions
- Glioblastoma, Glioma, Astrocytoma
- Being tested
- Functional MRI, FDG-PET, Structural MRI
- Keywords
- Primary brain tumor
- Medical subject headings
- Glioblastoma, Glioma, Astrocytoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Functional MRIDiagnostic test
11 minutes of Functional MRI alternating breathing Air-Room and gaz mix (5%CO2 21%O2 74%N2).
All procedure are acquired simultaneously on a single acquisition on the PET/MRI camera in the institution.
FDG-PETDiagnostic test
Some patients who did not benefit from a FDG-PET in their clinical evaluation or more than 1 month before the inclusion in the present study will be ask to also undergo a brain FDG-PET , the dose is set at 2 Mega becquerel per Kg.
All procedure are acquired simultaneously on a single acquisition on the PET/MRI camera in the institution.
Structural MRIDiagnostic test
Patient will benefit Different anatomical sequence of acquisition listed here : T1 , T1 with contrast agent (gadovist) , T2 flair , T2 and DSC (Dynamic susceptibility contrast) , and Time Of Flight .
All procedure are acquired simultaneously on a single acquisition on the PET/MRI camera in the institution.
| Study group | Role | What they receive |
|---|---|---|
| Glioma patient | Experimental | As compared to the pre-surgical evaluation that brain tumor patients routinely undergo in our institution, patients are asked to undergo some additional examinations. Receives: Diagnostic Test: Functional MRI; Diagnostic Test: FDG-PET; Diagnostic Test: Structural MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of Hypercapnia administration on fMRI data
For brain fRMI data: BOLD signal variation (Arbitrary Unit from a percent change from baseline).
Measured: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
Effects of Hypercapnia administration on PET-FDG regional standardized data.
For brain PET-FDG: regional SUV value (Standardized Uptake Ratio) .The SUV is a mathematically derived ratio of tissue radioactivity concentration at a point in time at a specific region of interest and the injected dose of radioactivity per kilogram of the patient's body weight
Measured: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
Effects of Hypercapnia administration on PET-FDG global data
For brain PET-FDG: Statistical Parametric Mapping analysis (SPM) for voxel-wise comparison and multiple correlations (t-score)
Measured: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
Effects of Hypercapnia administration on oxygen saturation (SpO2)
SpO2 Variation: Measured in percentage points (%), reflecting the change from baseline levels.
Measured: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
End tidal CO2
End Tidal CO2 during the experiment allow the modelisation and quantification of MRI signal among brain tissue. End tidal CO2 pressure is measured in mmHg
Measured: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
Breathing Rate
Breathing Rate during the experiment allow the modelisation and quantification of MRI signal among brain tissue. Breathing rate is measure in respiration per minute
Measured: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
Regional Cerebral Blood Volume
CBV represents the volume of blood present in 100 grams of brain tissue at a given time. It is used to assess the vascular capacity of the brain. unit are in mL per 100g of brain tissue .A DSC (Dynamic susceptibility contrast) -MRI is needed, the sequence involves the intravenous injection of a contrast agent, usually gadolinium-based. The contrast agent passes through the brain, and changes in the MRI signal are recorded over time.
Measured: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
Regional Cerebral Blood Flow
CBF measures the amount of blood flowing through 100 grams of brain tissue in one minute. This is a crucial measure for assessing cerebral perfusion and identifying areas of under- or hyperperfusion.(mL/100g/min)A DSC-MRI is needed, the sequence involves the intravenous injection of a contrast agent, usually gadolinium-based. The contrast agent passes through the brain, and changes in the MRI signal are recorded over time.
Measured: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
Secondary outcomes (5)
Tumor Grading
Tumor Grading, respectively with the World Health Organisation (WHO) 2021 guideline about brain neoplasm
Measured: up to 2 week after last acquisition to allow Multidisciplinary oncologic commission to fix the grading status
Tumor Histology
respectively with the WHO 2021 guideline about brain neoplasm from the surgery clinically planned
Measured: up to 2 week after last acquisition to allow Multidisciplinary oncologic commission to fix the grading status
Cerebrovascular reactivity mapping
Integration of the variation in fMRI signal and end tidal CO2, and breathing rate into a quantification . The produced data are in % of MRI signal change per mmHg of CO2
Measured: up to 1 month after the last acquisition to allow processing time , all the 40 patient together
Correlation map
Correlation on coregistration of fMRI and PET procedure among the brain and plotted in a linear regression. Correlation will be expressed in Spearman's "R".
Measured: up to 1 month after the last acquisition to allow processing time , all the 40 patient together
Functional connectivity
Measured on resting state data acquired during the experiment , allowing to construct a functional "FC" measure of the hub connected together in the brain. Measured in arbitrary unit.
Measured: up to 1 month after the last acquisition to allow processing time , all the 40 patient together
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2025
- Study start17 Feb 2025
- Primary completion13 Sep 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (34)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasme University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xavier De Tiège, MD,PhD, Study chair, Laboratoire de Neuroanatomie et Neuroimagerie translationnelles Université Libre de Bruxelles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06797661
- Sponsor's protocol ID
- SRB2024304
- Acronym
- NVUCVR
- Status last verified
- Sep 2026
- First submitted
- 23 Jan 2025
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Belanger M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 2011 Dec 7;14(6):724-38. doi: 10.1016/j.cmet.2011.08.016.
PubMed 22152301Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010 Nov 11;468(7321):232-43. doi: 10.1038/nature09613.
PubMed 21068832Koehler RC, Roman RJ, Harder DR. Astrocytes and the regulation of cerebral blood flow. Trends Neurosci. 2009 Mar;32(3):160-9. doi: 10.1016/j.tins.2008.11.005. Epub 2009 Jan 21.
PubMed 19162338Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem. 1977 May;28(5):897-916. doi: 10.1111/j.1471-4159.1977.tb10649.x. No abstract available.
PubMed 864466Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9868-72. doi: 10.1073/pnas.87.24.9868.
PubMed 2124706Sokoloff L. Relation between physiological function and energy metabolism in the central nervous system. J Neurochem. 1977 Jul;29(1):13-26. doi: 10.1111/j.1471-4159.1977.tb03919.x. No abstract available.
PubMed 407330Buxton RB. The physics of functional magnetic resonance imaging (fMRI). Rep Prog Phys. 2013 Sep;76(9):096601. doi: 10.1088/0034-4885/76/9/096601. Epub 2013 Sep 4.
PubMed 24006360Mueller WM, Yetkin FZ, Hammeke TA, Morris GL 3rd, Swanson SJ, Reichert K, Cox R, Haughton VM. Functional magnetic resonance imaging mapping of the motor cortex in patients with cerebral tumors. Neurosurgery. 1996 Sep;39(3):515-20; discussion 520-1. doi: 10.1097/00006123-199609000-00015.
PubMed 8875481Medina LS, Bernal B, Dunoyer C, Cervantes L, Rodriguez M, Pacheco E, Jayakar P, Morrison G, Ragheb J, Altman NR. Seizure disorders: functional MR imaging for diagnostic evaluation and surgical treatment--prospective study. Radiology. 2005 Jul;236(1):247-53. doi: 10.1148/radiol.2361040690.
PubMed 15987978Petrella JR, Shah LM, Harris KM, Friedman AH, George TM, Sampson JH, Pekala JS, Voyvodic JT. Preoperative functional MR imaging localization of language and motor areas: effect on therapeutic decision making in patients with potentially resectable brain tumors. Radiology. 2006 Sep;240(3):793-802. doi: 10.1148/radiol.2403051153. Epub 2006 Jul 20.
PubMed 16857981Fierstra J, Conklin J, Krings T, Slessarev M, Han JS, Fisher JA, Terbrugge K, Wallace MC, Tymianski M, Mikulis DJ. Impaired peri-nidal cerebrovascular reserve in seizure patients with brain arteriovenous malformations. Brain. 2011 Jan;134(Pt 1):100-9. doi: 10.1093/brain/awq286. Epub 2010 Nov 24.
PubMed 21109501Pillai JJ, Williams HT, Faro S. Functional imaging in temporal lobe epilepsy. Semin Ultrasound CT MR. 2007 Dec;28(6):437-50. doi: 10.1053/j.sult.2007.09.006.
PubMed 18075000Sunaert S. Presurgical planning for tumor resectioning. J Magn Reson Imaging. 2006 Jun;23(6):887-905. doi: 10.1002/jmri.20582.
PubMed 16649210Holodny AI, Schulder M, Liu WC, Wolko J, Maldjian JA, Kalnin AJ. The effect of brain tumors on BOLD functional MR imaging activation in the adjacent motor cortex: implications for image-guided neurosurgery. AJNR Am J Neuroradiol. 2000 Sep;21(8):1415-22.
PubMed 11003273Schreiber A, Hubbe U, Ziyeh S, Hennig J. The influence of gliomas and nonglial space-occupying lesions on blood-oxygen-level-dependent contrast enhancement. AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1055-63.
PubMed 10871013
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Insights Into the Pathophysiology of Neurovascular Uncoupling in Patients With Brain Lesions.
- ClinicalTrials.gov ID
- NCT06797661
- Acronym / sponsor ID
- NVUCVR / SRB2024304
- Conditions
- Glioblastoma, Glioma, Astrocytoma
- Keywords
- Primary brain tumor
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Erasme University HospitalUniversity, hospital or other
- Study start
- 17 Feb 2025 (actual)
- Primary completion
- 13 Sep 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 28 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neurovascular uncoupling (NVU) represents a major source of potential bias for the identification of eloquent brain regions through activation procedures in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI).
Same region shows proper pattern in glucose metabolism in victiny of brain lesions, investigated with positron emitted tomography with radiolabeled glucose (PET-FDG) This research project aims at investigating the mechanisms of NVU by using a multimodal noninvasive imaging approach in neurosurgical patients.
Detailed description
Brain metabolism and blood flow are tightly coupled with neuronal activity. Changes in neuronal activity result in the modulation of glucose consumption by neurons. Both glucose and lactate levels return to their baseline instantly as neuronal activity ceases, a phenomenon known as neurometabolic coupling. Given the limited energetic reserves in the central nervous system, neuronal activity heavily relies on the finely regulated supply of glucose from the bloodstream. However, the dynamic increase in cerebral blood flow (CBF) during neuronal activation far exceeds the increase in oxidative metabolism. This relative hyperemic response ensures an increased oxygen gradient between blood vessels and tissue, providing ample oxygen supply. The close temporal and regional link between changes in neuronal activity and CBF increase is referred to as neurovascular coupling (NVC) and involves a complex cascade of events. Neurotransmitters, such as glutamate, released at synapses bind to receptors on neurons and astrocytes, leading to the release of various chemical mediators, like nitric oxide and prostaglandins, which directly act on arterial smooth muscle tone. More complex and incompletely understood signaling pathways, including Na+ and Ca2+-mediated astrocyte signaling mechanisms, are also presumed to contribute to NVC.
The tight relationship between neuronal activity and both regional blood flow and metabolism has provided the basis for non-invasive functional brain imaging methods, including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). PET using [18Fluor ]-fluorodeoxyglucose (FDG) is a technique based on the accumulation of metabolized FDG (i.e., FDG-6-phosphate) in the astrocyte-neuron complex, reflecting the level of glucose consumption. Since the seminal works of Sokoloff et al., glucose utilization is considered a valid, accurate, and quantitative indicator of the level of local neuronal activity within the brain. In contrast, fMRI, which relies on the blood oxygen level-dependent (BOLD) signal, provides indirect information about neuronal activity by investigating perfusion-related changes coupled with neuronal activity. In areas of increased CBF due to modulations in neuronal activity, oxygen delivery exceeds the rate of oxygen utilization, inducing a local increase in the oxy-/deoxy-hemoglobin ratio. This leads to a detectable increase in the magnetic-susceptibility weighted MRI signal.
One of the earliest and still recognized clinical applications of fMRI has been preoperative functional mapping of the primary sensorimotor cortex in patients with brain tumors. This technique has significantly impacted surgical planning, often enabling more aggressive approaches than those considered without functional localization. fMRI has also been increasingly used in the presurgical evaluation of patients with vascular or epileptogenic lesions. However, despite the growing use of BOLD fMRI in patients with brain lesions, this technique has major limitations that must be considered when interpreting fMRI results in such populations. The main limitation is the impairment of BOLD signal changes due to lesion-related loss of normal vascular coupling with neuronal activity, a phenomenon referred to as neurovascular uncoupling (NVU). This can result in false-negative or false-positive results in critical eloquent cortex. If neuronal activity is preserved in diseased but viable cortex, NVU is presumed to occur due to astrocytic, neurotransmitter, or vascular dysfunction.
NVU has been mainly reported in patients with high-grade glial tumors and meningiomas. In such patients, the volume of task-based fMRI signal increases has been shown to be reduced adjacent to the tumor compared to homologous fMRI signal changes in the contralesional hemisphere, despite the absence of neurological deficit. In line with experimental data in healthy subjects showing that BOLD signal may decrease as cerebral blood volume (CBV) increases, impaired cerebrovascular reactivity (CVR) in brain tumor patients may be explained by changes in local perfusion. In hypervascularized tumors such as high-grade gliomas and meningiomas, local hyperperfusion has been suggested to explain the decreased BOLD signal on task-based fMRI. However, recent studies have demonstrated that NVU may also occur in low-grade gliomas. Given the absence of hyperperfusion in this tumor type, different mechanisms need to be considered. In low-grade gliomas, the observed NVU is currently thought to be, at least in part, due to disruption of astrocyte-vascular coupling (gliovascular uncoupling). Patients with arteriovenous malformations may exhibit impaired peri-nidal cerebrovascular reserve due to high-flow shunting, making perfusion-dependent mapping signals unreliable. Epilepsy patients may also exhibit regional impairment of CVR due to dramatic increases in brain metabolism and CBF during the ictal period, disruption of the brain-blood barrier, and an acute loss of cerebral pressure autoregulation.
According to previous research, CVR can be studied through the "hypercapnia challenge" during fMRI recordings, including breath-hold fMRI (BH fMRI) and carbogen inhalation fMRI. Hypercapnia is a potent vasodilator that increases the BOLD baseline signal by detecting an increase in tissue oxygenation resulting from increases in CBF while oxidative metabolism demands are considered to remain constant. However, the influence of hypercapnia on neural activity and neurometabolic/neurovascular couplings is not well understood and remains debated. In practice, areas of reduced or absent hypercapnia-induced increase in fMRI signal on CVR maps compared to homologous contralateral activation are assumed to indicate NVU. Recent studies suggest potential advantages in using resting-state (rs) fMRI as a preoperative technique. rs-fMRI is a functional neuroimaging technique that allows the measurement of spontaneous brain activity in patients at rest. Spontaneous BOLD signal fluctuations are highly correlated in distinct and long-ranged brain regions, indicating functional connectivity within specific and highly organized neuroanatomical networks. Functional connectivity studies have also demonstrated a high degree of spatial correlation between rs-fMRI functional brain connectivity and those studied during a hypercapnia challenge. Interestingly, recent research suggests that rs-BOLD signal may be impaired in patients in whom task-based increases in fMRI signals are reduced or absent due to NVU. Therefore, alterations in functional brain connectivity studied with rs-fMRI might provide insights into the presence of NVU as studied with CVR during hypercapnia. Such findings would be of interest in clinical practice as they could avoid the need for CVR-mapping with a hypercapnia challenge.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Glioma patient | Experimental | Diagnostic Test: Functional MRI, Diagnostic Test: FDG-PET, Diagnostic Test: Structural MRIAs compared to the pre-surgical evaluation that brain tumor patients routinely undergo in our institution, patients are asked to undergo some additional examinations. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients in the study include prior imaging showing a potentially resectable intra-cerebral mass lesion. Patient has to be included before surgery, chemotherapy and radiation
Key exclusion criteria (7 listed)
- previous brain surgery
- respiratory failure
- Asthma
- Claustrophobia
- Previous adverse reaction to gadovist (contrast agent)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Functional MRI11 minutes of Functional MRI alternating breathing Air-Room and gaz mix (5%CO2 21%O2 74%N2). All procedure are acquired simultaneously on a single acquisition on the PET/MRI camera in the institution. | Diagnostic test | Glioma patient |
| FDG-PETSome patients who did not benefit from a FDG-PET in their clinical evaluation or more than 1 month before the inclusion in the present study will be ask to also undergo a brain FDG-PET , the dose is set at 2 Mega becquerel per Kg. All procedure are acquired simultaneously on a single acquisition on the PET/MRI camera in the institution. | Diagnostic test | Glioma patient |
| Structural MRIPatient will benefit Different anatomical sequence of acquisition listed here : T1 , T1 with contrast agent (gadovist) , T2 flair , T2 and DSC (Dynamic susceptibility contrast) , and Time Of Flight . All procedure are acquired simultaneously on a single acquisition on the PET/MRI camera in the institution. | Diagnostic test | Glioma patient |
Primary outcome
Effects of Hypercapnia administration on fMRI data
Time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
For brain fRMI data: BOLD signal variation (Arbitrary Unit from a percent change from baseline).
Effects of Hypercapnia administration on PET-FDG regional standardized data.
Time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
For brain PET-FDG: regional SUV value (Standardized Uptake Ratio) .The SUV is a mathematically derived ratio of tissue radioactivity concentration at a point in time at a specific region of interest and the injected dose of radioactivity per kilogram of the patient's body weight
Effects of Hypercapnia administration on PET-FDG global data
Time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
For brain PET-FDG: Statistical Parametric Mapping analysis (SPM) for voxel-wise comparison and multiple correlations (t-score)
Effects of Hypercapnia administration on oxygen saturation (SpO2)
Time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
SpO2 Variation: Measured in percentage points (%), reflecting the change from baseline levels.
End tidal CO2
Time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
End Tidal CO2 during the experiment allow the modelisation and quantification of MRI signal among brain tissue. End tidal CO2 pressure is measured in mmHg
Breathing Rate
Time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
Breathing Rate during the experiment allow the modelisation and quantification of MRI signal among brain tissue. Breathing rate is measure in respiration per minute
Regional Cerebral Blood Volume
Time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
CBV represents the volume of blood present in 100 grams of brain tissue at a given time. It is used to assess the vascular capacity of the brain. unit are in mL per 100g of brain tissue .A DSC (Dynamic susceptibility contrast) -MRI is needed, the sequence involves the intravenous injection of a contrast agent, usually gadolinium-based. The contrast agent passes through the brain, and changes in the MRI signal are recorded over time.
Regional Cerebral Blood Flow
Time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)
CBF measures the amount of blood flowing through 100 grams of brain tissue in one minute. This is a crucial measure for assessing cerebral perfusion and identifying areas of under- or hyperperfusion.(mL/100g/min)A DSC-MRI is needed, the sequence involves the intravenous injection of a contrast agent, usually gadolinium-based. The contrast agent passes through the brain, and changes in the MRI signal are recorded over time.
5 secondary outcomes
Tumor Grading
Time frame: up to 2 week after last acquisition to allow Multidisciplinary oncologic commission to fix the grading status
Tumor Histology
Time frame: up to 2 week after last acquisition to allow Multidisciplinary oncologic commission to fix the grading status
Cerebrovascular reactivity mapping
Time frame: up to 1 month after the last acquisition to allow processing time , all the 40 patient together
Correlation map
Time frame: up to 1 month after the last acquisition to allow processing time , all the 40 patient together
Functional connectivity
Time frame: up to 1 month after the last acquisition to allow processing time , all the 40 patient together
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xavier De Tiège, MD,PhD study chair
Laboratoire de Neuroanatomie et Neuroimagerie translationnelles Université Libre de Bruxelles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Functional MRI, FDG-PET and Structural MRI in people with Glioblastoma and Glioma, run by Erasme University Hospital at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thibault Vanbutsele (25558167 ext. +32, thibault.vanbutsele@hubruxelles.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of Hypercapnia administration on fMRI data (time frame: end of acquisition ( group of 40 subject estimated at 10 months after first subjet acquisition)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06797661, which also lists 34 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.