An observational study in High-Grade Glioma, Glioblastoma and Brain Tumor Adult, sponsored by IRCCS Ospedale San Raffaele. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-15.
Sponsored by IRCCS Ospedale San Raffaele · Observational
High-grade gliomas are the most common primary malignant brain tumors and are characterized by infiltration of the surrounding brain tissue beyond the visible tumor margins. This infiltrative growth represents a major challenge for treatment planning and contributes to tumor recurrence. Conventional magnetic resonance imaging (MRI) is limited in its ability to distinguish tumor infiltration from non-tumoral changes such as vasogenic edema in the peri-tumoral region.
This prospective single-center observational study aims to improve the characterization of the peri-tumoral microenvironment in patients with suspected high-grade gliomas using advanced MRI techniques, including amide proton transfer-weighted (APTw) imaging and diffusion tensor imaging (DTI). These techniques provide complementary information about tissue composition and microstructure and may help identify areas of tumor infiltration that are not visible on conventional imaging.
APTw- and DTI-derived maps will be combined to generate imaging-derived maps describing the likelihood of tumor infiltration within the peri-tumoral region. These maps will be compared with histopathological findings obtained from tissue samples collected during biopsy or tumor resection performed as part of standard clinical care. Histological analyses will include assessment of tumor cellularity using hematoxylin and eosin staining and additional immunohistochemical markers routinely used in neuropathological evaluation. Patients will undergo routine clinical follow-up and the prognostic significance of the imaging-derived map will be assessed.
The overall goal of the study is to develop and validate imaging-based biomarkers capable of identifying infiltrated tissue within the peri-tumoral region. These findings may contribute to improved diagnostic accuracy and support future treatment planning strategies in patients with high-grade gliomas.
High-grade gliomas (HGGs) are among the most aggressive primary brain tumors in adults and are characterized by diffuse infiltration into the surrounding brain tissue. This infiltrative behavior represents one of the main limitations to complete surgical removal and contributes to tumor recurrence.
Accurate identification of infiltrated tissue beyond the visible tumor margins remains a major challenge in neuro-oncology. Conventional magnetic resonance imaging (MRI) sequences, including contrast-enhanced T1-weighted imaging and fluid-attenuated inversion recovery (FLAIR), are routinely used to define tumor boundaries. However, non-contrast-enhancing regions often contain a mixture of tumor infiltration and vasogenic edema, which cannot be reliably distinguished using standard imaging alone. Improved imaging techniques capable of characterizing the biological properties of the peri-tumoral microenvironment are therefore needed to support more accurate assessment of tumor extent. Advanced MRI techniques provide complementary information about tissue composition and microstructure. Diffusion tensor imaging (DTI) provides information related to tissue organization and cellular architecture through the measurement of water diffusion properties. Amide proton transfer-weighted (APTw) imaging provides information related to endogenous mobile proteins and peptides, which are typically increased in tumor tissue and reflect metabolic and molecular changes. The combined use of these techniques may improve the identification of tumor-infiltrated tissue within regions that appear non-enhancing on conventional MRI.
This study is designed as a prospective, single-center observational study enrolling adult patients with radiologically suspected high-grade gliomas who are scheduled to undergo biopsy or tumor resection as part of standard clinical care. All enrolled participants will undergo a preoperative MRI examination that includes both standard clinical sequences and advanced imaging sequences, including diffusion tensor imaging (DTI) and amide proton transfer-weighted (APTw) imaging. Following imaging acquisition, patients will undergo neurosurgical procedures according to clinical indications. Tissue samples collected during biopsy or tumor resection will undergo standard histopathological evaluation as part of routine diagnostic care. Histological analyses will include assessment of tumor cellularity using hematoxylin and eosin staining and additional immunohistochemical markers.
Imaging data derived from APTw and DTI will be combined to generate maps describing the likelihood of tumor infiltration within the peri-tumoral region. These imaging-derived maps aim to represent spatial variations in tissue characteristics that reflect differences in tumor cellularity. A central objective of the study is the correlation between imaging-derived features and histopathological findings, to validate the maps. Tissue samples obtained during surgery will be spatially related to corresponding imaging locations, allowing comparison between imaging-derived measures and histological characteristics. This approach is intended to validate imaging-derived estimates of tumor infiltration against histological reference standards.
In addition to baseline imaging and histopathological correlation, patients will undergo routine postoperative follow-up according to clinical practice. Follow-up MRI examinations will be analyzed to evaluate patterns of tumor recurrence and to explore the spatial relationship between imaging-derived features identified at baseline and subsequent sites of tumor progression. Moreover the prognostic significance of the area of tumor infiltration described by the imaging-derived map will be evaluated.
The overall objective of this study is to develop and validate imaging-based biomarkers capable of identifying infiltrated tissue beyond the visible tumor margins through integration of advanced MRI techniques, histopathological correlation, and longitudinal follow-up. Improved identification of infiltrated tissue may contribute to a better understanding of tumor growth patterns and support future advances in surgical planning and treatment strategies in patients with high-grade gliomas.
2,132 studies on the registry are indexed under Glioblastoma; 464 are open to participants now.
This study's planned enrollment of 20 is below the median of 60 across 208 observational studies indexed under Glioblastoma.
Browse Glioblastoma studies →IRCCS Ospedale San Raffaele is the lead sponsor of 36 studies on the registry; 28 are open to participants now.
Compared within Glioblastoma, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Glioma. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Adult patients (≥18 years) with radiologically suspected, treatment-naïve high-grade gliomas undergoing standard-of-care neurosurgical procedures (stereotactic biopsy or surgical resection) and pre-operative MRI evaluation will be prospectively enrolled. All participants will receive routine clinical management and follow-up according to standard clinical practice.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
to MRI because of:
I. Claustrophobia II. Presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants) III. Sickle cell disease IV. Renal failure or reduced renal function, as determined by (GFR) \< 30 mL/min/1.73 m\^2 based on a serum creatinine level obtained within 40 days prior to registration
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adult patients with suspected high-grade glioma undergoing standard-of-care MRI evaluation and neurosurgical procedures (stereotactic biopsy or surgical resection). Imaging data and tissue samples will be collected and analyzed to investigate imaging biomarkers of tumor infiltration.
Diagnostic Test: Standard-of-care MRI data, including APT and diffusion imaging, will be analyzed to generate quantitative maps of tumor infiltration within the peri-tumoral region.
Advanced MRI data acquired as part of standard-of-care imaging, including amide proton transfer (APT) and diffusion tensor imaging (DTI), will be processed using dedicated post-hoc image analysis pipelines. A habitat-based clustering approach combining APT-derived MTRasym and DTI-derived mean diffusivity maps will be applied to generate a quantitative Tumor Infiltration Probability Map (TIPM). This imaging biomarker will be used to characterize peri-tumoral tissue heterogeneity and investigate tumor infiltration patterns for research purposes only.
Correlation Between TIPM Values and Tumor Cell Density
Correlation coefficients between voxel-wise Tumor Infiltration Probability Map (TIPM) values within the non-contrast-enhancing tumor component and tumor cell density (cells/mm²) measured on hematoxylin and eosin-stained histological sections.
Time frame: At the time of surgery
Correlation Between TIPM Values and Ki-67 Proliferation Index
Correlation coefficients between voxel-wise Tumor Infiltration Probability Map (TIPM) values within the non-contrast-enhancing tumor component and Ki-67 proliferation index measured on histological sections.
Time frame: At the time of surgery
Spatial Overlap Between TIPM-Defined Tumor Infiltration and Tumor Recurrence
Spatial overlap, measured using the Dice similarity coefficient, between baseline TIPM-defined tumor infiltration volume and tumor recurrence segmented on follow-up MRI.
Time frame: At the time of radiological recurrence (according to RANO criteria)
Association Between TIPM-Derived Tumor Infiltration Volume and Survival Outcomes
Hazard ratio for progression-free survival (PFS) and overall survival (OS) associated with TIPM-derived tumor infiltration volume. PFS and OS are defined as time from surgery to disease progression or death.
Time frame: From the date of surgery up to 36 months
No study locations are listed for this record.
Plan to share: No — Individual participant data will not be shared due to institutional data protection policies and the sensitive nature of clinical and imaging data.
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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IRCCS Ospedale San Raffaele