APT-weighted and Diffusion MRI for Characterizing Tumor Infiltration in High-Grade Gliomas

NCT07532031 | Not Yet Recruiting

• 1 other identifier: APT_HGG_26
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Glioblastoma; High-Grade Glioma; Brain Tumor Adult

Keywords

Amide Proton Transfer Imaging; Diffusion Tensor Imaging; Imaging Biomarkers; High-grade glioma; Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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.

  At the time of surgery

Secondary Outcomes (3)

• Correlation Between TIPM Values and Ki-67 Proliferation Index

  At the time of surgery

• Spatial Overlap Between TIPM-Defined Tumor Infiltration and Tumor Recurrence

  At the time of radiological recurrence (according to RANO criteria)

• Association Between TIPM-Derived Tumor Infiltration Volume and Survival Outcomes

  From the date of surgery up to 36 months

Study Arms (1)

Patients with radiologically suspected, treatment-naïve high-grade gliomas

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.

Interventions

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. DIAGNOSTIC_TEST

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.

Patients with radiologically suspected, treatment-naïve high-grade gliomas

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Adult patients (both male and female, \>= 18 years old)
• Previously acquired MRI suggestive for the presence of high-grade glioma
• Treatment-naïve status, defined as no prior surgical, radiotherapeutic, or systemic oncological treatment for the index brain lesion.
• Indication for biopsy or tumor resection
• Willingness to participate to the study and ability to sign informed consent

You may not qualify if:

• Pregnancy (to be excluded through a human chorionic gonadotropin pregnancy test performed on urine or serum when childbearing potential) and / or lactation.
• Contraindications 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 Glomerular Filtration Rate (GFR) \< 30 mL/min/1.73 m\^2 based on a serum creatinine level obtained within 40 days prior to registration
• Presence of any other co-existing condition (such as serious systemic illness, including uncontrolled intercurrent infection, uncontrolled malignancy, significant renal or hepatic disease, or psychiatric/social situations) which might, in the judgment of the investigator, increase the risks to the subject or limit compliance with study requirements
• Inability to undergo surgical procedures
• Severe hepatic impairment, defined as the presence of two or more of the following parameters (assessed within 40 days): bilirubin ≥3 mg/dL, albumin \<2.8 g/dL, International normalized ratio \>2.3 with no history of anticoagulant therapy, platelet count \< 100 109/L, AST ≥ 400 U/L, ALT ≥400 U/L, presence of ascites.

Sponsors & Collaborators

• IRCCS Ospedale San Raffaele: lead
• Fondazione Umberto Veronesi: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue samples obtained during standard-of-care neurosurgical procedures (stereotactic biopsy or surgical resection) will be retained.

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

Diffusion Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Magnetic Resonance Imaging; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Central Study Contacts

Gianluca Nocera, MD, PhD

CONTACT

0039 0226433007; nocera.gianluca@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 15, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share