Ralf B. Loeffler

R2* magnetic resonance imaging of the liver in patients with iron overload

R2* magnetic resonance imaging (R2*-MRI) can quantify hepatic iron content (HIC) by noninvasive means but is not fully investigated. Patients with iron overload completed 1.5T R2*-MRI examination and liver biopsy within 30 days. Forty-three patients (sickle cell anemia, n = 32; beta-thalassemia major, n = 6; and bone marrow failure, n = 5) were analyzed: median age, 14 years, median transfusion duration, 15 months, average (+/-SD) serum ferritin 2718 plus or minus 1994 ng/mL, and average HIC 10.9 plus or minus 6.8 mg Fe/g dry weight liver. Regions of interest were drawn and analyzed by 3 independent reviewers with excellent agreement of their measurements (intraclass correlation coefficient = 0.98). Ferritin and R2*-MRI were weakly but significantly associated (range of correlation coefficients among the 3 reviewers, 0.41-0.48; all P < .01). R2*-MRI was strongly associated with HIC for all 3 reviewers (correlation coefficients, 0.96-0.98; all P < .001). This high correlation confirms prior reports, calibrates R2*-MRI measurements, and suggests its clinical utility for predicting HIC using R2*-MRI. This study was registered at www.clinicaltrials.gov as #NCT00675038.

Ventricular diastolic dysfunction in sickle cell anemia is common but not associated with myocardial iron deposition

Cardiac failure from myocardial iron deposition is a severe complication in patients with transfusion‐related iron overload. Progressive heart damage from iron overload can cause left ventricular systolic and diastolic dysfunction in patients with hematologic disorders. Since nontransfused patients with sickle cell anemia (SCA) have a high incidence of diastolic dysfunction, we investigated the relationships among transfusional iron burden, myocardial iron deposition, and diastolic ventricular dysfunction by T2*‐MRI and tissue Doppler echocardiography in iron‐overloaded children with SCA.

Evaluation of respiratory liver and kidney movements for MRI navigator gating

To determine the tracking factor by studying the relationship between kidney and diaphragm motions and to compare the efficiency of the gating‐and‐following and gating‐only algorithms in reducing motion artifacts in navigator‐gated scans.

MR imaging assessment of tumor perfusion and 3D segmented volume at baseline, during treatment, and at tumor progression in children with newly diagnosed diffuse intrinsic pontine glioma

BACKGROUND AND PURPOSE: DIPG is among the most devastating brain tumors in children, necessitating the development of novel treatment strategies and advanced imaging markers such as perfusion to adequately monitor clinical trials. This study investigated tumor perfusion and 3D segmented tumor volume as predictive markers for outcome in children with newly diagnosed DIPG. METHODS: Imaging data were assessed at baseline, during, and after RT, and every other month thereafter until tumor progression for 35 patients (ages 2–16 years) with newly diagnosed DIPG enrolled in the phase I clinical study, NCT00472017. Patients were treated with conformal RT and vandetanib, a vascular endothelial growth factor receptor 2 inhibitor. RESULTS: Tumor perfusion increased and tumor volume decreased during combined RT and vandetanib therapy. These changes slowly diminished in follow-up scans until tumor progression. However, increased tumor perfusion and decreased tumor volume during combined therapy were associated with longer PFS. Apart from a longer OS for patients who showed elevated tumor perfusion after RT, there was no association for tumor volume and other perfusion variables with OS. CONCLUSIONS: Our results suggest that tumor perfusion may be a useful predictive marker for the assessment of treatment response and tumor progression in children with DIPG treated with both RT and vandetanib. The assessment of tumor perfusion yields valuable information about tumor microvascular status and its response to therapy, which may help better understand the biology of DIPGs and monitor novel treatment strategies in future clinical trials.

Simultaneous field and R2 mapping to quantify liver iron content using autoregressive moving average modeling.

To investigate the use of a complex multigradient echo (mGRE) acquisition and an autoregressive moving average (ARMA) model for simultaneous susceptibility and R  2* measurements for the assessment of liver iron content (LIC) in patients with iron overload.

Improved renal perfusion measurement with a dual navigator‐gated Q2TIPS fair technique

A dual navigator‐gated, flow‐sensitive alternating inversion recovery (FAIR) true fast imaging with steady precession (True‐FISP) sequence has been developed for accurate quantification of renal perfusion. FAIR methods typically overestimate renal perfusion when respiratory motion causes the inversion slice to move away from the imaging slice, which then incorporates unlabeled spins from static tissue. To overcome this issue, the dual navigator scheme was introduced to track inversion and imaging slices, and thus to ensure the same position for both slices. Accuracy was further improved by a well‐defined bolus length, which was achieved by a modification version of Q2TIPS (quantitative imaging of perfusion using a single subtraction, second version with interleaved thin‐slice TI1 periodic saturation): a series of saturation pulses was applied to both sides of the imaging slice at a certain time after the inversion. The dual navigator‐gated technique was tested in eight volunteers. The measured renal cortex perfusion rates were between 191 and 378 mL/100 g/min in the renal cortex with a mean of 376 mL/100 g/min. The proposed technique may prove most beneficial for noncontrast‐based renal perfusion quantification in young children and patients who may have difficulty holding their breath for prolonged periods or are sedated/anesthetized. Magn Reson Med, 2010.

Quantitative ultrashort echo time imaging for assessment of massive iron overload at 1.5 and 3 Tesla

Hepatic iron content (HIC) quantification via transverse relaxation rate (R2*)‐MRI using multi‐gradient echo (mGRE) imaging is compromised toward high HIC or at higher fields due to the rapid signal decay. Our study aims at presenting an optimized 2D ultrashort echo time (UTE) sequence for R2* quantification to overcome these limitations.

Does fat suppression via chemically selective saturation affect R2*‐MRI for transfusional iron overload assessment? A clinical evaluation at 1.5T and 3T

Fat suppression (FS) via chemically selective saturation (CHESS) eliminates fat–water oscillations in multiecho gradient echo (mGRE) R2*‐MRI. However, for increasing R2* values as seen with increasing liver iron content (LIC), the water signal spectrally overlaps with the CHESS band, which may alter R2*. We investigated the effect of CHESS on R2* and developed a heuristic correction for the observed CHESS‐induced R2* changes.

Evaluation of SWI in Children with Sickle Cell Disease

A sample of 21 patients with sickle cell disease were assessed with SWI and compared with controls. The MRI findings were correlated with hematologic parameters. Venous volumes were lower in the SCD group but not associated with the hematologic parameters included in this study. Arterial hypointensity was seen in nearly all patients with SCD. Quantitation of venous volume with SWI may be useful for the assessment of cerebrovascular pathology in patients with SCD. BACKGROUND AND PURPOSE: SWI is a powerful tool for imaging of the cerebral venous system. The SWI venous contrast is affected by blood flow, which may be altered in sickle cell disease. In this study, we characterized SWI venous contrast in patients with sickle cell disease and healthy control participants and examined the relationships among SWI venous contrast, and hematologic variables in the group with sickle cell disease. MATERIALS AND METHODS: A retrospective review of MR imaging and hematologic variables from 21 patients with sickle cell disease and age- and sex-matched healthy control participants was performed. A Frangi vesselness filter was used to quantify the attenuation of visible veins from the SWI. The normalized visible venous volume was calculated for quantitative analysis of venous vessel conspicuity. RESULTS: The normalized visible venous volume was significantly lower in the group with sickle cell disease vs the control group (P < .001). Normalized visible venous volume was not associated with hemoglobin, percent hemoglobin F, percent hemoglobin S, absolute reticulocyte count, or white blood cell count. A hypointense arterial signal on SWI was observed in 18 of the 21 patients with sickle cell disease and none of the 21 healthy control participants. CONCLUSIONS: This study demonstrates the variable and significantly lower normalized visible venous volume in patients with sickle cell disease compared with healthy control participants. Decreased venous contrast in sickle cell disease may reflect abnormal cerebral blood flow, volume, velocity, or oxygenation. Quantitative analysis of SWI contrast may be useful for investigation of cerebrovascular pathology in patients with sickle cell disease, and as a tool to monitor therapies. However, future studies are needed to elucidate physiologic mechanisms of decreased venous conspicuity in sickle cell disease.

Radial Ultrashort TE Imaging Removes the Need for Breath-Holding in Hepatic Iron Overload Quantification by R2* MRI

OBJECTIVE The objective of this study is to evaluate radial free-breathing (FB) multiecho ultrashort TE (UTE) imaging as an alternative to Cartesian FB multiecho gradient-recalled echo (GRE) imaging for quantitative assessment of hepatic iron content (HIC) in sedated patients and subjects unable to perform breath-hold (BH) maneuvers. MATERIALS AND METHODS FB multiecho GRE imaging and FB multiecho UTE imaging were conducted for 46 test group patients with iron overload who could not complete BH maneuvers (38 patients were sedated, and eight were not sedated) and 16 control patients who could complete BH maneuvers. Control patients also underwent standard BH multiecho GRE imaging. Quantitative R2* maps were calculated, and mean liver R2* values and coefficients of variation (CVs) for different acquisitions and patient groups were compared using statistical analysis. RESULTS FB multiecho GRE images displayed motion artifacts and significantly lower R2* values, compared with standard BH multiecho GRE images and FB multiecho UTE images in the control cohort and FB multiecho UTE images in the test cohort. In contrast, FB multiecho UTE images produced artifact-free R2* maps, and mean R2* values were not significantly different from those measured by BH multiecho GRE imaging. Motion artifacts on FB multiecho GRE images resulted in an R2* CV that was approximately twofold higher than the R2* CV from BH multiecho GRE imaging and FB multiecho UTE imaging. The R2* CV was relatively constant over the range of R2* values for FB multiecho UTE, but it increased with increases in R2* for FB multiecho GRE imaging, reflecting that motion artifacts had a stronger impact on R2* estimation with increasing iron burden. CONCLUSION FB multiecho UTE imaging was less motion sensitive because of radial sampling, produced excellent image quality, and yielded accurate R2* estimates within the same acquisition time used for multiaveraged FB multiecho GRE imaging. Thus, FB multiecho UTE imaging is a viable alternative for accurate HIC assessment in sedated children and patients who cannot complete BH maneuvers.