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. Fortythree patients (sickle cell anemia, n ‫؍‬ 32; ␤-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. IntroductionMonitoring body iron content is critical for clinical management of patients with iron overload. Prior reports of iron measurements by R2 magnetic resonance imaging (MRI) and R2*-MRI relaxometry in the liver have shown good correlations with hepatic iron content (HIC). 1-3 However, MRI calibration varies according to instrumentation and technique. To calibrate the R2*-MRI technique for noninvasive HIC assessment, we conducted a study to estimate the correlation of R2*-MRI with liver biopsy-proven HIC determination in patients with iron overload. Methods PatientsPatients 7 years of age and older with iron overload (ferritin Ͼ 1000 ng/mL within 3 months of enrollment or Ն 18 erythrocyte transfusions) were eligible. All participants underwent nonsedated liver MRI examination and ferritin measurement, followed within 30 days by liver biopsy with HIC determination. The St Jude Children's Research Hospital Institutional Review Board provided continuing approval, and all participants or legal guardians signed informed consent in accordance with the Declaration of Helsinki. Liver biopsiesTwo liver specimens were obtained, the first for liver iron quantitation (Mayo Laboratories, Rochester MN) and the second for pathology review. All histology was reviewed by a single pathologist blinded to clinical status and HIC values. Liver fibrosis was scored from zero (absent fibrosis) to 6 (cirrhosis). 4 MRI techniqueThe single breath-hold R2*-MRI used a 1.5T MRI scanner (Siemens Symphony, Siemens; Malvern, PA) using a multiecho gradient echo sequence to acquire 20 images with increasing echo times (range, 1.1-17.3 ms). Liver images were obtained in transversal slice orientation through the center at the main portal vein origin. Slice thickness measured 10 mm with in-plane resolution of 3.125 mm. Quantitative T2* maps were calculated offline using custom-...

A novel method is presented to simultaneously measure the permeability surface area product of water (PS), also known as capillary diffusion capacity, and the regional blood volume (RBV). It is based on magnetic resonance imaging of the longitudinal relaxation times of tissue and blood at different concentrations of an intravascular MR contrast agent. PS and RBV were measured in vivo in different regions of the brain and the skeletal muscle of the rat. The average PS values (n = 5) obtained in cerebral cortex, corpus callosum, hippocampus, thalamus, jaw muscle, and tongue muscle were 3.31 +/- 0.20, 1.81 +/- 0.25, 3.37 +/- 0.36, 3.68 +/- 0.44, 10.6 +/- 1.1, and 14.1 +/- 2.51 ml x min(-1) x g(-1), respectively. The corresponding average RBV values were 1.63 +/- 0.18, 1.22 +/- 0.25, 3.30 +/- 0.37, 3.03 +/- 0.36, 1.66 +/- 0.30, and 1.38 +/- 0.33 ml x 100 g(-1). These results are in good agreement with previously reported literature values obtained by means of autoradiography.

In this contribution, a rapid and robust technique for quantitative T(1) mapping of the human lung is presented. Based on a series of Snapshot FLASH tomograms acquired after a single inversion pulse, high quality and quantitative T(1) parameter maps acquired in under five seconds were obtained from six healthy volunteers. The measured T(1) values are in good agreement with previously reported literature values. T(1) maps were also acquired with the volunteers breathing room air or 100% O(2). The T(1) difference between breathing room air and 100% O(2) is statistically significant at P < 0.0001.

BackgroundPreclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system.Principal FindingsHere we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a “standard of care” chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents.SignificanceThe studies suggest that use of both the TH-NMYC model of neuroblastoma and the orthotopic xenograft model provide the optimal combination for testing new chemotherapies for this devastating childhood cancer.

Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.