Ferumoxytol Enhanced Hyperfine Low Field Strength MRI

Evaluation of Hyperfine Low Field Strength Portable Point-of-Care Magnetic Resonance Imaging System in Patients Receiving Ferumoxytol Infusions

The purpose of this pilot study is to evaluate the feasibility of using Ferumoxytol as a contrast agent on a low field strength, portable magnetic resonance imaging (MRI) system. Participants receiving Ferumoxytol as part of routine clinical care for iron deficiency anemia will be recruited and scanned on the Hyperfine MRI system before and after their clinically scheduled intravenous infusion. Resultant images will be compared to assess signal intensity changes generated by the presence of Feromoxytol.

Study Overview

• Status: Completed
• Conditions: Anemia, Hemolytic
• Intervention / Treatment: Device: Hyperfine Portable MRI

Detailed Description

Ferumoxytol is a superparamagnetic iron oxide nanoparticle (SPION) preparation that was originally designed as an MRI contrast agent, but later received FDA approval as a treatment for iron deficiency anemia. Contrast agents alter MR images by changing tissue magnetic relaxation constants such as T1 and T2 (or T2*). Gadolinium-based contrast agents decrease T1 values, causing increased signal on T1-weighted images. At low field strength, T1 values are already very short so a further decrease may provide little contrast. At typical field strengths, Ferumoxytol strongly decreases T1 and also T2 (and T2*) values, increasing signal on T1-weighted images and (conversely) decreasing signal on T2-weighted images. This T2-based contrast mechanism may be maintained at lower field strength.

Patients with iron deficiency anemia are commonly prescribed Ferumoxytol periodically as part of their standard clinical care. Multiple studies have characterized the efficacy and safety of Ferumoxytol in the treatment of iron deficiency anemia. Patients prescribed Ferumoxytol for iron-deficiency anemia typically include otherwise healthy women with heavy menstrual periods, patients with inflammatory bowel disease, and patients with chronic kidney disease. Such patients make ideal candidates for characterizing the effects of Ferumoxytol on novel imaging devices by obviating a medically unnecessary injection of the contrast agent.

Contrast agents play a key role in diagnosing and managing numerous diseases. Ferumoxytol has been used to image a variety of pathologies and organs, including tumors and inflammation in the brain, liver, pancreas, and prostate. In addition to the different magnetic relaxation properties described above, Ferumoxytol has a higher molecular weight and prolonged blood pool period compared to typical gadolinium-based agents, facilitating imaging vasculature prior to the contrast agent leaking into the extravascular tissue. This has been exploited at higher field strengths and may be particularly advantageous for low field imaging that requires longer scan times. Ferumoxytol iron particles are taken up through the reticuloendothelial system and added to physiologic iron stores, rather than being excreted through the kidneys, resulting in increased plasma half-life while also avoiding concerns related to impaired renal function that sometimes arise with other contrast agents.

The Hyperfine device is a newly developed MRI unit that has multiple potential advantages over standard CT or MRI including portability, easier upkeep, open design, and ease of use. Unlike CT, the Hyperfine device does not use moving parts or X-rays to generate images. Unlike routine MRI, the Hyperfine device uses two permanent magnets with open space between and around them, rather than a super-cooled superconducting magnetic tube. In contrast to CT and routine MRI, the device can be wheeled from place to place and moved into position with the patient remaining on a gurney or hospital bed. Relative to routine MRI, the device uses a very low magnetic field strength of 64 mT compared to 1.5 T or 3 T, making it safer for patients or environments with medical devices having metallic components.

Standard images of different types are obtained on the Hyperfine device at the push of a button on an attached touch pad. Imaging protocols include those for anatomical depiction such as balance steady-state free precession (bSFFP), T1-weighted (T1W) gradient echo (GRE), and fast low-angle shot (FLASH) as well as imaging methods focused on the detection of pathology and tissue damage such as diffusion-weighted imaging (DWI), fluid attenuated inversion recovery (FLAIR), and T2-weighted (T2W) fast spin echo (FSE). However, it is not known if existing contrast agents can provide effective contrast in the Hyperfine low-field MRI.

Thus, the primary purpose of this study is to evaluate the efficacy of Ferumoxytol as a contrast agent in low-field MRI scanners. Patients who are already receiving Ferumoxytol as a treatment for iron deficiency anemia will be scanned before and after Ferumoxytol infusion. Degree of contrast enhancement in intravascular and extravascular compartments including the cerebral vasculature and the brain parenchyma will be the primary end-point for the study.

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects referred from the Hematology Oncology Department, scheduled to receive an intravenous infusion of Ferumoxytol as part of their standard of care (SOC) treatment for iron deficiency anemia will receive one Hyperfine MRI scan of the brain prior to their infusion and one Hyperfine MRI scan of the brain after their infusion.

Description

Inclusion Criteria:

• Age 18 years or older
• Prescribed Ferumoxytol for iron deficiency anemia
• Informed consent obtained from patient or a legally authorized representative

Exclusion Criteria:

1. Contraindications to routine 1.5 T MRI evaluation, including:

   • Electrical implants such as cardiac pacemakers or perfusion pumps
   • Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts or heart valves with steel parts, metal fragments, shrapnel, tattoos near the eye, steel implants, or other irremovable ferromagnetic objects
   • History of uncontrolled seizures
   • Claustrophobia
   • Weight greater than or equal to 400 lbs (181.4 kg)
2. Pregnancy
3. Inability or suspected inability to comply with the study procedures

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients prescribed Ferumoxytol for iron deficiency anemia; Patients with iron deficiency anemia are commonly prescribed Ferumoxytol periodically as part of their standard clinical care. Multiple studies have characterized the efficacy and safety of Ferumoxytol in the treatment of iron deficiency anemia. Patients prescribed Ferumoxytol for iron-deficiency anemia typically include otherwise healthy women with heavy menstrual periods, patients with inflammatory bowel disease, and patients with chronic kidney disease. Such patients make ideal candidates for characterizing the effects of Ferumoxytol on novel imaging devices by obviating a medically unnecessary injection of the contrast agent.

Device: Hyperfine Portable MRI; The Hyperfine device is a newly developed MRI unit that has multiple potential advantages over standard CT or MRI including portability, easier upkeep, open design, and ease of use. Unlike CT, the Hyperfine device does not use moving parts or X-rays to generate images. Unlike routine MRI, the Hyperfine device uses two permanent magnets with open space between and around them, rather than a super-cooled superconducting magnetic tube. In contrast to CT and routine MRI, the device can be wheeled from place to place and moved into position with the patient remaining on a gurney or hospital bed. Relative to routine MRI, the device uses a very low magnetic field strength of 64 mT compared to 1.5 T or 3 T, making it safer for patients or environments with medical devices having metallic components.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contrast enhancement	Changes in MRI signal intensity (contrast enhancement) produced by the presence of the Ferumoxytol contrast agent will be quantified by co-registering brain MRI studies obtained before and after administration of Ferumoxytol and determining the ratio of signal intensity values between the two sets of images (post-Ferumoxytol/pre-Ferumoxytol) in regions of interest placed separately over brain parenchyma or vascular structures. Based on the magnetic properties of Ferumoxytol, this contrast ratio is expected to be greater than one for T1-weighted scans and less than one for T2- or T2*-weighted scans.	2 thirty-five minute scans

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Actual): August 29, 2022
• Study Completion (Actual): August 29, 2022

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Estimate): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Anemia; Feraheme; Ferumoxytol; Infusion
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Anemia, Hemolytic
• Other Study ID Numbers: 842634

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