Massive Iron Deposit Assessment

Not Applicable

Completed

Conditions: Excessive Body Iron Burden
Iron Overload

Interventions: Device: R2*-UTE
Device: R2*-GRE
Procedure: Liver biopsy

Registration Number: NCT01572922

Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary: Iron overload is a severe complication of multiple blood transfusions. As the body has no physiologic mechanism for clearing iron, repeated transfusions cause iron accumulation in organs and lead to iron toxicity. Accurate assessment of iron overload is paramount to quantify excessive iron accumulation and to monitor response to iron chelation therapy. Magnetic resonance imaging (MRI) methods have been used to noninvasively measure hepatic iron concentration (HIC). Although MRI-based measurements of transverse relaxation rates (R2 and R2\*) accurately predict biopsy-proven HICs below 15 mg Fe/g, previous studies have shown that their precision is limited for HICs above 15 mg Fe/g and inaccurate above 25 mg Fe/g. Current R2\* gradient-echo (GRE) MR techniques fail occasionally for very high iron overloads (HIC \~ 15-25 mg Fe/g) and always for massive iron overloads (HIC \> 25 mg Fe/g) because R2\* is so high that the MR signal decays before it can be measured accurately.

Overall accrual: 200 patients

Purpose: To determine if a new MRI (UTE) can measure the amount of iron in the liver of people with large amounts of iron and compare the results with the same patient's liver bx. Estimated patient accrual is 150. It is estimated that 41 of these patients will have clinical indication for liver biopsy.

Detailed Description: The MIDAS study is a prospective and non-therapeutic study that will test a new MRI technique for the assessment of iron overload in the liver: the newly developed ultra short echo time (UTE), R2\*-UTE. The R2\*-UTE technique, developed by St. Jude investigators from the Department of Radiological Sciences, will be first tested in healthy volunteers for feasibility and implementation of the technique. The technique will then be tested in research participants, who will have both the R2\*-GRE and the R2\*-UTE techniques performed, in addition to a liver biopsy for liver iron quantitation if clinically indicated. Quantitation of liver tissue iron will be done at Mayo Clinic Laboratory in Rochester, Minnesota.

Primary Objective:

* To test the association of hepatic iron content (HIC) measured with the newly developed 1.5T R2\*-UTE technique and HIC quantified by liver biopsy in subjects with iron overload.

Secondary Objectives:

* To explore the relationship between 1.5T R2\*-UTE and 1.5T R2\*-GRE measurements in subjects with iron overload.

* To explore the relationship between 1.5T R2\*-UTE measurements with iron studies (serum iron and transferrin saturation) in subjects with iron.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 142

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Iron-overloaded	Liver biopsy	Patients with iron overload or excessive body iron burden, a serious condition resulting from increased dietary gastro¬intestinal absorption, multiple erythrocyte transfusions, or both. Interventions: R2\-UTE, R2\-GRE, and if clinically indicated, liver biopsy.
Iron-overloaded	R2*-UTE	Patients with iron overload or excessive body iron burden, a serious condition resulting from increased dietary gastro¬intestinal absorption, multiple erythrocyte transfusions, or both. Interventions: R2\-UTE, R2\-GRE, and if clinically indicated, liver biopsy.
Iron-overloaded	R2*-GRE	Patients with iron overload or excessive body iron burden, a serious condition resulting from increased dietary gastro¬intestinal absorption, multiple erythrocyte transfusions, or both. Interventions: R2\-UTE, R2\-GRE, and if clinically indicated, liver biopsy.

Primary Outcome Measures

Name	Time	Method
Hepatic Iron Content in the Liver Using Liver Biopsy	up to 30 days after MRI	Hepatic iron content in the liver using liver biopsy
MRI-derived R2* Values Using 1.5T UTE Technique	Up to 30 days after MRI	Hepatic iron content of the liver using MRI-derived 1.5T R2\-UTE measurement, with results in Hz. R2\ is a measure obtained with MRI, i.e., MRI R2\. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every "picture taken", this signal is strong in the beginning and then wanes off. R2\ reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\= 1/T2\). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\, the more iron in the liver tissue. We can compare the R2\ value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.

Secondary Outcome Measures

Name	Time	Method
Transferrin Saturation Measurements	Up to 30 days after MRI	Iron Transferrin Saturation in % measurements Transferrin Saturation measurements from eligible patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.
MRI-derived R2* Using 1.5T GRE Technique	Up to 30 days after MRI	MRI-derived R2\* Using 1.5T GRE Technique in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every "picture taken", this signal is strong in the beginning and then wanes off. R2\ reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\= 1/T2\). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\, the more iron in the liver tissue. We can compare the R2\ value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.
MRI Derived R2* Using 1.5T UTE Technique	up to 30 days after MRI	MRI-derived R2\* value using 1.5T R2\-UTE in Hz. R2\ is a measure obtained with MRI, i.e., MRI R2\. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every "picture taken", this signal is strong in the beginning and then wanes off. R2\ reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\= 1/T2\). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\, the more iron in the liver tissue. We can compare the R2\ value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.
R2* Using 1.5T UTE Technique for Patients With Serum Iron and Transferrin Saturation Measurements	Up to 30 days after MRI	MRI-derived R2\* value using 1.5T R2\-UTE in Hz for patients who have had serum iron and transferrin saturation measurements. R2\ is a measure obtained with MRI, i.e., MRI R2\. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every "picture taken", this signal is strong in the beginning and then wanes off. R2\ reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\= 1/T2\). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\, the more iron in the liver tissue. We can compare the R2\ value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.
Serum Iron Measurements Compared With 1.5T R2* UTE	Up to 30 days after MRI	Serum iron measurements from eligible patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.