Development of MRF for Characterization of Brain Tumors After Radiotherapy

Development of Magnetic Resonance Fingerprinting for Characterization of Brain Tumors After Radiotherapy

The purpose of this study is to discover the potential convenience and ease of using a Magnetic Resonance Imaging (MRI) technique, named Magnetic Resonance Fingerprinting (or MRF), to achieve high-quality images within a short scan time of 5 min for viewing the entire brain. This is an advanced quantitative assessment of brain tissues. This method is being applied with IVIM MRI to be able to tell the difference between a brain with radiation necrosis and a brain with tumor recurrence. Participants will consist of individuals who have received radiation therapy in the past and were diagnosed with radiation necrosis, individuals with recurrent tumors, individuals with previously untreated tumors, and healthy individuals who have no brain diseases and have not had radiation treatment to the brain. Participants will undergo an MRI scan at a one-time research study visit; no extra tests or procedures will be required for this research study.

The primary objectives of this study are:

• To demonstrate the clinical feasibility of combining MRF with state-of-the-art parallel imaging techniques to achieve high-resolution quantitative imaging within a reasonable scan time of 5 min for whole brain coverage.
• To apply the developed quantitative approach in combination with IVIM MRI for differentiation of tumor recurrence and radiation necrosis.
• To investigate the effect of radiation dose on the development of radiation necrosis and tumor recurrence.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Brain Tumor; Brain Metastases; Brain Necrosis
• Intervention / Treatment: Procedure: MRF in conjunction with IVIM MRI without contrast

Detailed Description

Although Stereotactic radiosurgery (SRS) is utilized as an effective treatment method, after several months to over 1 year following SRS, 33% of treated brain metastases increase in size on imaging, which is suspicious for tumor progression. However, based on findings in follow-up biopsies, the majority of newly detected metastases on imaging are radiation treatment effects instead of active tumor. So far, the only gold standard to differentiate active tumor and radiation necrosis is surgical resection for pathologic confirmation, which is invasive, not favored for poor surgical candidates, and should be avoided in cases of necrosis. The existing clinical imaging techniques have poor sensitivity or specificity in differentiating these two types of tissues. Recently, a novel MRI data acquisition approach, namely MR Fingerprinting (MRF), has been introduced for the simultaneous measurement of multiple important parameters in a single MRI scan. In addition, quantitative diffusion MRI, such as the intravoxel incoherent motion (IVIM) technique, can provide a noninvasive and powerful tool to quantify microstructural information by measuring water diffusion and microcirculation perfusion in vivo. This study aims to demonstrate the clinical feasibility of combining MRF with state-of-the-art parallel imaging techniques to achieve high-resolution quantitative imaging within a reasonable scan time of 5 min for whole brain coverage. It also aims to apply the developed quantitative approach in combination with IVIM MRI for the differentiation of tumor recurrence and radiation necrosis. The multi-parametric quantitative measures developed in this study could establish a new fundamental biomarker for the diagnosis and monitoring of brain tumors.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lan Lu, PhD; Phone Number: 1-866-223 8100; Email: TaussigResearch@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
      • Contact: Chaitra A Badve, MD
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Taussig Cancer Center
      • Principal Investigator: Lan Lu, PhD
      • Principal Investigator: Samuel Chao, MD
      • Contact: Lan Lu, PhD; Phone Number: 866-223-8100

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Healthy Participants:

• Ages 18 - 60
• No history of cerebrovascular disease
• No cognitive impairments
• Able to provide informed consent

Inclusion Criteria for Participants with Brain Tumors:

• Biopsy-proven cases of developed recurrent tumor or radiation necrosis, OR
• a. PET identified with developed recurrent tumor or radiation necrosis. OR
• b. Highly suspicious case with developed recurrent tumor or radiation necrosis confirmed by tumor board, attending physician or surgeon.
• ECOG performance status 0-2.
• Life expectancy > 6 months.
• Participant with other sites of extracranial metastatic disease or any prior or current systemic therapies will be considered and evaluated by the investigators of the study on a subject basis.

Inclusion Criteria for Participants with Brain Metastases or Primary Gliomas:

• Radiology identified with developed primary gliomas tumor or brain metastases, OR
• a. PET identified with developed gliomas tumor or brain metastases, OR
• b. Highly suspicious case with developed gliomas tumor or brain metastases confirmed by tumor board
• Participants must not have received prior radiation or surgical treatment for brain metastases or primary glioma.
• Age: 18 years and over
• ECOG performance status 0-2
• Life expectancy > 6 months.
• Participant with other sites of extracranial metastatic disease or any prior or current systemic therapies will be considered and evaluated by the investigators of the study on a subject basis.

Inclusion Criteria for Participants with Meningiomas:

• Radiology identified with resectable meningioma
• Participants have no prior radiation or surgical treatment for brain lesions
• Age: 18 years or older
• ECOG performance status 0-2
• Life expectancy > 6 months.
• Participants with other sites of extracranial metastatic disease or any prior or current systemic therapies will be considered and evaluated by the investigators of the study on a subject basis.

Exclusion Criteria:

• Pregnant women OR lactating women
• Participants with ferromagnetic or otherwise non-MRI compatible aneurysm clips.
• Participants who cannot go into the MRI scanner due to metal implants and other medical conditions.
• The presence of an implanted medical device that is not MRI-compatible, including, but not limited to: pacemaker, defibrillator.
• Participants with contraindications for MRI due to embedded foreign metallic objects such as bullets, shrapnel, metalwork fragments, or other metallic material.
• Known history of severe claustrophobia.
• Participants unable to lay still in the scanner for 30 minutes at a time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteer Participants; Healthy volunteers will be recruited to evaluate the capability of MRF in conjunction with intravoxel incoherent motion (IVIM) MRI and serve as healthy control data to compare with the participant data.	Procedure: MRF in conjunction with IVIM MRI without contrast; MRF in conjunction with IVIM MRI scan, without contrast.
Experimental: Participants with Radiation Necrosis; The MRI scans (MRF and IVIM) will be performed on participants with newly developed necrosis prior to any further therapy implementation, surgical biopsy, or resection. For the participants undergoing surgical biopsy or resection after the MRI scans, the findings from the analysis of pathological biopsied specimen will serve as pathological confirmation for the MRI imaging findings	Procedure: MRF in conjunction with IVIM MRI without contrast; MRF in conjunction with IVIM MRI scan, without contrast.
Experimental: Participants with Tumor Recurrence; The MRI scans (MRF and IVIM) will be performed on participants with newly developed recurrent prior to any further therapy implementation, surgical biopsy, or resection. For the participants undergoing surgical biopsy or resection after the MRI scans, the findings from the analysis of pathological biopsied specimen will serve as pathological confirmation for the MRI imaging findings	Procedure: MRF in conjunction with IVIM MRI without contrast; MRF in conjunction with IVIM MRI scan, without contrast.
Experimental: Participants with Brain Metastases; The MRI scans (MRF and IVIM) will be performed on participants with newly developed, untreated brain metastases prior to any therapy implementation, surgical biopsy, or resection. For the participants undergoing surgical biopsy or resection after the MRI scans, the findings from the analysis of pathological biopsied specimen will serve as pathological confirmation for the MRI imaging findings	Procedure: MRF in conjunction with IVIM MRI without contrast; MRF in conjunction with IVIM MRI scan, without contrast.
Experimental: Participants with Primary Gliomas; The MRI scans (MRF and IVIM) will be performed on participants with newly developed, untreated primary gliomas prior to any therapy implementation, surgical biopsy, or resection. For the participants undergoing surgical biopsy or resection after the MRI scans, the findings from the analysis of pathological biopsied specimen will serve as pathological confirmation for the MRI imaging findings	Procedure: MRF in conjunction with IVIM MRI without contrast; MRF in conjunction with IVIM MRI scan, without contrast.
Experimental: Participants with Meningiomas; The MRI scans (MRF and IVIM) will be performed on participants with meningiomas who have not yet undergone radiation or surgical treatment. For the participants undergoing surgical biopsy or resection after the MRI scans, the findings from the analysis of pathological biopsied specimen will serve as pathological confirmation for the MRI imaging findings	Procedure: MRF in conjunction with IVIM MRI without contrast; MRF in conjunction with IVIM MRI scan, without contrast.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of T1 relaxation times	The primary objective is to use MRF and IVIM MRI to demonstrate clinical feasibility and differentiation of tumor recurrence and radiation necrosis. This will be measured by the 3D-MRF T1 relaxation times. The difference in mean T1 between each cohort of participants will be measured.	Within the total 30-45 minute scan time
Comparison of T2 relaxation times	The primary objective is to use MRF and IVIM MRI to demonstrate clinical feasibility and differentiation of tumor recurrence and radiation necrosis. This will be measured by the 3D-MRF T2 relaxation times. The difference in mean T2 between each cohort of participants will be measured.	Within the total 30-45 minute scan time
Comparison of proton density maps	The primary objective is to use MRF and IVIM MRI to demonstrate clinical feasibility and differentiation of tumor recurrence and radiation necrosis. This will be measured by comparing the MRF proton density maps of each cohort of participants. This will be compared using a t-test.	Within the total 30-45 minute scan time
Comparison of water diffusion in brain tissues	The primary objective is to use MRF and IVIM MRI to demonstrate clinical feasibility and differentiation of tumor recurrence and radiation necrosis. This will be measured by comparing the diffusion parameters measured by the IVIM method between the three cohorts of participants. This will be compared using a t-test.	Within the total 30-45 minute scan time
Comparison of blood perfusion in brain tissues	The primary objective is to use MRF and IVIM MRI to demonstrate clinical feasibility and differentiation of tumor recurrence and radiation necrosis. This will be measured by comparing the perfusion parameters measured by the IVIM method between the three cohorts of participants. This will be compared using a t-test.	Within the total 30-45 minute scan time
Comparison of MRF imaging tool in different participant populations	The objective is to compare the effects of radiation dose on development of radiation and necrosis and tumor recurrence by comparing participants in all cohorts (healthy participants with no brain disease, participants with brain tumors (treated), participants with brain metastases or primary gliomas (previously untreated)). The predictive ability will be assessed by comparing univariable ROC analysis, quantified using area under the curve (AUC).	Within the total 30-45 minute scan time

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: The Cleveland Clinic
• Investigators: Principal Investigator: Samuel Chao, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center; Principal Investigator: Lan Lu, PhD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: October 20, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Radiation necrosis; Magnetic Resonance Fingerprinting
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Glioma; Brain Neoplasms; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Diagnostic Uses of Chemicals; Contrast Media
• Other Study ID Numbers: CASE3323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No