Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Breast Neoplasms

Mitral Valve Insufficiency

Breast Diseases

Skin Diseases

Patients undergo measurement of tumor perfusion and permeability using DCE-MRI, tumor cellularity using DW-MRI, phospholipid metabolism using 31P MRS, macromolecular content using MT-MRI, and cellular protein content using CEST-MRI. All of these procedures are integrated into a single MRI exam lasting under 60 min.

high field strength magnetic resonance imaging

magnetic resonance spectroscopic imaging

chemical exchange saturation transfer magnetic resonance imaging

diffusion-weighted magnetic resonance imaging

dynamic contrast-enhanced magnetic resonance imaging

Thomas Yankeelov

This pilot clinical trial studies ultra-high field magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques in diagnosing breast cancer. New diagnostic procedures may be a more sensitive way to detect breast cancer.

PRIMARY OBJECTIVES:

I. To implement quantitative dynamic contrast-enhanced (DCE)-MRI, diffusion-weighted (DW)-MRI, 31 phosphorus (31P) MRS, magnetization transfer (MT)-MRI, chemical exchange saturation transfer (CEST)-MRI, and high-resolution structural imaging at 7 Tesla in patients for diagnosing breast tumors.

OUTLINE:

Patients undergo measurement of tumor perfusion and permeability using DCE-MRI, tumor cellularity using DW-MRI, phospholipid metabolism using 31P MRS, macromolecular content using MT-MRI, and cellular protein content using CEST-MRI. Diagnostic performance of one, or a combination, of these metrics will be investigated in the context of breast cancer.

Ultra High Field MRI and MRS Techniques in Diagnosing Breast Cancer

Ultra-High Field (7 Tesla) MRI/MRS Evaluation of Breast Cancer

Ninety-percent simultaneous confidence rectangles for sensitivity and specificity will be constructed at the 25th, 50th (median), and 75th percentiles of the model predicted probability of disease.

A generalized linear mixed models analysis of variance with a logit link will be used to predict pathological disease status from MRI and MRS parameters.

National Cancer Institute (NCI)

Vanderbilt-Ingram Cancer Center

Director of Cancer Imaging Research, Vanderbilt University Institute of Imaging Science (VUIIS); Associate Professor of Radiology and Radiological Sciences, Biomedical Engineering, Physics and Astronomy, and Cancer Biology;

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Hematinics

Pharmaceutical Solutions

All Drugs and Chemicals

Ferrosoferric Oxide

Parenteral Nutrition Solutions

Patients receive gadolinium IV on day 1 and ferumoxytol non-stoichiometric magnetite IV on day 2. Patients undergo anatomical MRI sequences with 3T or 7T at baseline and on days 1-3. Patients also undergo DSC MRI and DCE MRI on days 1-2. Day 1 and day 2 imaging sessions may be separated by up to 7 days.

3 Tesla Magnetic Resonance Imaging

Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Ferumoxytol

Gadolinium

High Field Strength Magnetic Resonance Imaging

Susceptibility Weighted Imaging

Edward Neuwelt

This phase II trial studies how well magnetic resonance imaging (MRI) using contrast imaging agent ferumoxytol works in comparison to standard imaging agent gadolinium in measuring tumors in patients undergoing treatment for brain tumors or other tumors that have spread to the brain. Diagnostic procedures, such as MRI, may help find and diagnose disease and find out how far the disease has spread. MRI scans use radio waves and a powerful magnet linked to a computer to create detailed pictures of areas inside the body. The contrast imaging agent ferumoxytol consists of small iron particles taken by the blood stream to the brain and to the area of the tumor. It is highly visible on the MRI, and may help visualize the blood flow going through the tumor better than gadolinium can. Using a more sensitive and faster 7 Tesla (7T) magnet MRI in conjunction with a contrast imaging agent may provide a better way to measure tumors than the 3 Tesla (3T) magnet MRI in patients with brain tumors.

PRIMARY OBJECTIVES:

I. To compare quantitative blood brain barrier permeability measurements (derived transfer coefficient \[Ktrans\]) of a standard gadolinium (Gd) MRI contrast agent at 3T and 7T using dynamic contrast enhancement (DCE) MRI.

II. To compare dynamic susceptibility contrast (DSC) based perfusion measures at 3T and 7T.

SECONDARY OBJECTIVES:

I. To describe the blood brain barrier permeability to ferumoxytol (ferumoxytol non-stoichiometric magnetite) and to a standard gadolinium-based MRI contrast agent using signal intensity changes as described above.

II. To describe cerebral blood volume (CBV) measurements obtained using a standard gadolinium MRI contrast agent and ferumoxytol.

III. To evaluate tumor microvascularity on susceptibility-weighted images (SWI).

IV. To describe the microscopic distribution of ferumoxytol particles in tissue removed from subjects undergoing surgery.

OUTLINE: Patients are assigned to 3T or 7T magnet within the subgroups.

Patients receive gadolinium intravenously (IV) on day 1 and ferumoxytol non-stoichiometric magnetite IV on day 2. Patients undergo anatomical MRI sequences with 3T or 7T at baseline and on days 1-3. Patients also undergo DSC MRI and DCE MRI on days 1-2. Day 1 and day 2 imaging sessions may be separated by up to 7 days.

After completion of study, patients are followed up at approximately 4-6 weeks.

Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors

A Phase II Study of Ferumoxytol and Gadolinium Magnetic Resonance Imaging at 3T and 7T in Subjects With Primary or Metastatic Brain Tumors Either Before or After Therapy

Paired sample t-tests will be used for primary descriptive comparisons. Secondary analyses will use a repeated measures analysis of variance (ANOVA) model to compare 3T and 7T while adjusting for other factors including tumor type, prior therapy, and, potentially, important baseline factors that differ between the subjects assigned to the two field strengths. Normality will be assessed graphically and, if needed, a transformation (e.g. the logarithmic transform) will be applied.

A two sample t-test was used for primary descriptive comparisons since CNR was measured on different subjects at 3T and 7T. There were no repeated measures in the resulting data. Given the small sample size, a linear regression was conducted to compare CNR between 3T and 7T only adjusted for Fe dose. No other adjusted analyses were conducted.

CNR was compared between 3T and 7T for both Ferumoxytol and Gadolinum. Ferumoxytol was administered using three injections and CNR was measured after each injection, thus we have three measures of CNR (Fe1CNR, Fe2CNR and Fe3CNR).

Mixed model repeated measures ANOVAs will be fit. Factors will include imaging agent (Gd or ferumoxytol) and field strength (3T and 7T). Each subject will contribute one measure for each combination of imaging agent and field strength (4 measures total).

Blood volumes will be compared using repeated measures ANOVA to compare the imaging agents.

Analysis will also include covariates of prior therapy. For the comparisons between treated and untreated subjects, means and confidence intervals will be estimated for each group for the perfusion and permeability measures and for the baseline characteristics.

The pathology will be analyzed qualitatively for the presence of iron staining. The amount and localization of the staining will be assessed, with attention paid to whether the tumor cells themselves or reactive cells in and around the tumor demonstrate iron uptake.

Oregon Health and Science University

OHSU Knight Cancer Institute

Principal Investigator

A subset of subjects with primary or metastatic brain tumors will be assigned to 3 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 3 Tesla MRI scanner.

Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 3 Tesla in Subjects With Brain Tumors

A subset of subjects with primary or metastatic brain tumors will be assigned to 7 Tesla MRI and will undergo gadolinium enhanced imaging on day 1, ferumoxytol enhanced imaging on day 2, and a non contrast ("post-ferumoxytol") imaging on day 3. All scans will be performed on a 7 Tesla MRI scanner.

Gadolinium and Ferumoxytol Magnetic Resonance Imaging at 7 Tesla in Subjects With Brain Tumors

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Glioblastoma

Anaplastic astrocytoma

Astrocytoma grade II

Anaplastic oligodendroglioma

Oligodendroglioma grade II

Meningioma

Metastasis

CNS lymphoma

Other

Brain tumor type

Amy Huddleston

The first primary objective was to use dynamic contrast enhancement (DCE) MRI. Due to limitations of the scanners, these images were not collected. Dynamic susceptibility contrast (DSC) images were collected which are reported in the second primary objective.

Contrast to Noise Ratio (CNR), in Terms of Normalized Signal Intensity Changes, for T1-weighted MRI Signal at 3T and 7T (Gadolinium [Gd] T1-weighted Magnetic Resonance Imaging [MRI] DCE Data Only)

Ferumoxytol 1st dose

Ferumoxytol 2nd dose

Ferumoxytol 3rd dose

Other patients were excluded due to poor DSC graph or no residual tumor for measurement or residual tumor stayed within vascular lumen. Non-contrast (day 3) data not collected.

CNR, in Terms of Normalized Signal Intensity Changes, for Dynamic Susceptibility Contrast (DSC) MRI Data Sets at 3T and 7T (Gadolinium and Ferumoxytol)

Data for secondary outcomes were not collected. The study was terminated early as the 7t scanner was not providing the images needed, and we did not have the funding to continue.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ultra High Field MRI and MRS Techniques in Diagnosing Breast Cancer	NCT01938651	Breast Cancer	high field stre... magnetic resona... chemical exchan... diffusion-weigh... dynamic contras...	18 Years -	Vanderbilt-Ingram Cancer Center
Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors	NCT00659126	Metastatic Mali... Primary Brain N...	3 Tesla Magneti... Dynamic Contras... Dynamic Suscept... Ferumoxytol Gadolinium High Field Stre... Susceptibility ...	18 Years -	OHSU Knight Cancer Institute

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