Development and Validation of Advanced MRI Methods for Clinical Applications

September 20, 2021 updated by: Lisa Arnold, St. Joseph's Hospital and Medical Center, Phoenix
A critical aspect of brain tumor patient management is the radiographic assessment of tumor status, which is used for diagnosis, localization, surgical planning and surveillance. The primary goal is to develop and apply advanced, quantitative magnetic resonance imaging (MRI) techniques that can supplement existing high-resolution anatomic imaging to aid clinical decision-making for patients diagnosed with brain tumors. The studies proposed herein involve the development of advanced imaging methods that are intrinsically sensitive to the biophysical characteristics associated with tumor pathogenesis, as they are more likely to improve tumor characterization and localization and may offer early and more specific indicators of treatment response. These advanced methods include diffusion-weighted imaging (DWI), chemical exchange saturation transfer (CEST), and dynamic susceptibility contrast (DSC) perfusion MRI. A secondary objective of this study is to validate cerebral blood volume (CBV) metrics acquired using a DSC acquisition and post-processing methods by comparison with an intravascular reference standard contrast agent. Validated perfusion imaging techniques will improve the reliability and relevancy of derived CBV metrics across a range of clinical applications, including tumor localization, treatment guidance, therapy response assessment, surgical and biopsy guidance, and multi-site clinical trials of conventional and targeted brain tumor therapies.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The objectives of this study are to (1) Develop and optimize acquisition methods for MRI-based biomarkers that are indicative of brain tumor pathophysiology. These methods include, but are not limited to, DWI, CEST, and Dynamic Susceptibility Contrast (DSC) and Dynamic Contrast Enhanced (DCE) MRI; and (2) Validate DSC-MRI accuracy by comparison to an intravascular reference standard. Developmental studies: During the development of new imaging-based biomarkers, it is critical to optimize acquisition parameters, systematically characterize performance and contrast in the pathology of interest, validate with histopathology and establish test-retest repeatability. Thus, the first goal of this study is to develop advanced Diffusion Weighted Imaging (DWI), CEST and DSC/DCE-MRI methods for application to brain tumors. Objective 1 is a single-center study of up to 60 subjects being done to explore and optimize imaging signatures indicative of altered functional tumor states. These advanced imaging methods will allow the investigators to probe neuropathological tumor correlates, including cellular characteristics, molecular and metabolic changes, and vascular characteristics. Compared to existing conventional anatomic imaging, the researchers hypothesize that these experimental methods will be better able to characterize brain tumors and will have the potential to serve as new biomarkers of diagnostic and therapeutic importance. The researchers approach brings together biophysical and physiological information obtained from MRI and correlates this with clinical diagnoses and outcomes. Validation of DSC-MRI: Despite DSC-MRI's potential impact on clinical care, its broad scale integration has been slow, in large part from a lack of consensus about methodology and how to prevent potential CBV inaccuracies. Although DSC-MRI relies on the assumption that gadolinium-based contrast agents remain within the vascular lumen, this condition is often violated in vivo. If not corrected for, contrast agent leakage effects lead to CBV inaccuracy, misdiagnosis, and potentially mistreatment. While there exist numerous leakage correction strategies that have been shown to clearly improve DSC-MRI's clinical utility (e.g., predicting therapeutic response), a key limitation has prevented the standardization and wide-spread adoption of DSC-MRI methodology: To date, no study has validated the accuracy of leakage corrected CBV measures in patients. So while leakage corrected CBV values may be used, for example, to differentiate tumor recurrence from post-treatment effects, it is unknown whether this clinical benefit is a consequence of the complex combination of pulse sequence parameters, kinetics, dosing scheme, relaxivities, and leakage correction strategy or if the computed CBV actually reflects the underlying vascular density. This distinction is critical because it has implications for DSC-MRI standardization, establishing CBV thresholds for clinic use, multi-site comparisons and clinical trials. The investigators believe this limitation represents the most critical and clinically relevant challenge in the field of brain tumor DSC-MRI that urgently needs to be addressed. Objective 2 is a single-center study of up to 160 subjects being done to validate the accuracy of DSC-MRI measures of CBV. To validate the DSC-MRI measures derived from small molecular weight gadolinium-based (Gd) contrast agents, the investigators will compare rCBV maps to those derived from the intravascular contrast agent, Ferumoxytol. Ferumoxytol has been evaluated in humans as a potential DSC-MRI contrast agent but not for the purposes of validating leakage correction techniques. Since ferumoxytol-based DSC-MRI is not influenced by leakage effects, it enables the assessment of the most reliable perfusion metrics that can be expected from DSC-MRI and, as such, is the most reliable reference standard by which to evaluate CBV accuracy. Note that while ferumoxytol is undergoing clinical trials as a potential DSC-MRI contrast agent, it is unlikely to replace Gd-based contrast agents because it cannot provide the signal enhancement expected on conventional post-contrast T1-weighted images and is therefore unsuitable for use with standard response criteria.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
220

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Recruiting
        • St. Joseph's Hospital and Medical Center
        • Contact:
        • Principal Investigator:
          • C C Quarles, PhD
        • Sub-Investigator:
          • Ashley M Stokes, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must have either radiological or established histological diagnosis of the following: glioma / central nervous system (CNS) lymphoma / meningioma or brain metastases.
  • Willing and able to provide written informed consent in compliance with the regulatory requirements. If a subject is unable to provide written informed consent, written informed consent may be obtained from the subject's legal representative.
  • In the opinion of the investigator, able to fully participate in the study and sufficiently proficient in English to be capable of reliably completing study assessments.
  • Sexually active women of child-bearing potential (Groups 1 and 2) and men (Group 2 only) must agree to use adequate methods to avoid pregnancy.

Exclusion Criteria:

  • Subjects who have a contraindication for MRI: presence of an incompatible bio-implants (e.g., pacemakers, neurostimulators, electronic infusion pumps, etc.), metal in their bodies (non-MRI compatible cerebral aneurysm clips, shrapnel, metallic fragments in or near the eyes as pertains to metal workers and machinists), or noticeable anxiety and/or claustrophobia and/or severe vertigo when moved into the magnet bore.
  • Subjects who are pregnant or lactating or who suspect they might be pregnant.
  • (Groups 1 and 2, subjects receiving intravenous gadolinium (Gd) contrast material). Subjects with renal insufficiency or known allergy to Gd-based contrast material.
  • (Group 2 only) Subjects with known or suspected iron overload.
  • (Group 2 only) Subjects with known allergic or hypersensitivity reactions to parenteral iron treatment or other intravenous iron products; subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator's discretion.
  • Unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol.
  • Any other reasons that, in the opinion of the Investigator, the candidate is determined to be unsuitable for entry into the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Development of advanced MRI methods
Subjects with brain tumor. Subjects may be scanned using a single time-point to permit development and optimization of advanced MRI methods. Subjects may be scanned up to two times, with both visits occurring within one month, to permit analysis of test-retest reliability/repeatability.
Other: MRI
MRI scans to include: scout images, transmitter tuning, shimming, slice prescription - 5 min; conventional structural MRI; T1-weighted anatomic MRI scan - 7 min; and, T2-weighted anatomic MRI scan - 5 min. Advanced MRI to include: Diffusion Weighted MRI (DW-MRI) - 7 min; Chemical Exchange Saturation Transfer (CEST) - 9 min; Dynamic Susceptibility Contrast / Dynamic Contrast Enhanced MRI - 8 min; and, other advanced imaging, as needed, to be determined. Post-contrast conventional MRI to include T1-weighted anatomic MRI scan - 7 min. Repeat within 1 month.
Other: MRI
MRI scans to include: scout images, transmitter tuning, shimming, slice prescription - 5 min. Conventional structural MRI to include: T1-weighted anatomic MRI scan - 7 min; and, T2-weighted anatomic MRI scan - 5 min. Serial DSC-MRI: staged injections of Gd-based contrast and Ferumoxytol - 20 min. Post-contrast conventional MRI: T1-weighted anatomic MRI scan - 7 min.
Active Comparator: Validation of rCBV accuracy
64 subjects with primary glioma and 96 subjects with recurrent glioma. Subjects will be scanned using a single time-point to validate rCBV accuracy.
Other: MRI
MRI scans to include: scout images, transmitter tuning, shimming, slice prescription - 5 min; conventional structural MRI; T1-weighted anatomic MRI scan - 7 min; and, T2-weighted anatomic MRI scan - 5 min. Advanced MRI to include: Diffusion Weighted MRI (DW-MRI) - 7 min; Chemical Exchange Saturation Transfer (CEST) - 9 min; Dynamic Susceptibility Contrast / Dynamic Contrast Enhanced MRI - 8 min; and, other advanced imaging, as needed, to be determined. Post-contrast conventional MRI to include T1-weighted anatomic MRI scan - 7 min. Repeat within 1 month.
Other: MRI
MRI scans to include: scout images, transmitter tuning, shimming, slice prescription - 5 min. Conventional structural MRI to include: T1-weighted anatomic MRI scan - 7 min; and, T2-weighted anatomic MRI scan - 5 min. Serial DSC-MRI: staged injections of Gd-based contrast and Ferumoxytol - 20 min. Post-contrast conventional MRI: T1-weighted anatomic MRI scan - 7 min.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
cerebral blood volume
Time Frame: Within 60 days of MRI
In patients with brain tumors we will develop and optimize advanced MRI methods to characterize blood volume.
Within 60 days of MRI
the contrast agent extravasation rate constant (Ktrans, 1/min)
Time Frame: Within 60 days of MRI
In patients with brain tumors we will develop and optimize advanced MRI methods to characterize Ktrans
Within 60 days of MRI
Repeatability coefficient
Time Frame: within 60 days of MRI
will assess the repeatability of MRI
within 60 days of MRI

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Intraclass correlation coefficient
Time Frame: Within 60 days of MRI
Validate DSC-MRI accuracy by comparison to an intravascular reference standard by comparing rCBV maps to those derived from the intravascular contrast agent, Ferumoxytol
Within 60 days of MRI

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
St. Joseph's Hospital and Medical Center, Phoenix

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: C C Quarles, PhD, St. Joseph's Hospital and Medical Center, Phoenix
  • Principal Investigator: Ashley M Stokes, PhD, St. Joseph's Hospital and Medical Center, Phoenix

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 26, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 26, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 11, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 29, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 21, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PHXA-16-0235-10-08
  • 1R01CA213158-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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