Multislice Multiecho Research Articles

Assessment of Tumor Cell Invasion and Radiotherapy Response in Experimental Glioma by Magnetic Resonance Elastography.

Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient. This is a clinical dilemma, as recurrence can arise from MRI-occult glioma cell invasion. Tumor cell invasion, tumor growth and radiotherapy alter the brain parenchymal microstructure and thus are assessable by diffusion tensor imaging (DTI) and MR elastography (MRE). Experimental, animal model. Twenty-three male NMRI nude mice orthotopically implanted with S24 patient-derived glioma cells (experimental mice) and 9 NMRI nude mice stereotactically injected with 1 μL PBS (sham-injected mice). 2D and 3D T2-weighted rapid acquisition with refocused echoes (RARE), 2D echo planar imaging (EPI) DTI, 2D multi-slice multi-echo (MSME) T2 relaxometry, 3D MSME MRE at 900 Hz acquired at 9.4 T (675 mT/m gradient strength). Longitudinal 4-weekly imaging was performed for up to 4 months. Tumor volume was assessed in experimental mice (n = 10 treatment-control, n = 13 radiotherapy). The radiotherapy subgroup and 5 sham-injected mice underwent irradiation (3 × 6 Gy) 9 weeks post-implantation/sham injection. MRI-/MRE-parameters were assessed in the corpus callosum and tumor core/injection tract. Imaging data were correlated to light sheet microscopy (LSM) and histology. Paired and unpaired t-tests, a P-value ≤0.05 was considered significant. From week 4 to 8, a significant callosal stiffening (4.44 ± 0.22 vs. 5.31 ± 0.29 kPa) was detected correlating with LSM-proven tumor cell invasion. This was occult to all other imaging metrics. Histologically proven tissue destruction in the tumor core led to an increased T2 relaxation time (41.65 ± 0.34 vs. 44.83 ± 0.66 msec) and ADC (610.2 ± 12.27 vs. 711.2 ± 13.42 × 10-6 mm2/s) and a softening (5.51 ± 0.30 vs. 4.24 ± 0.29 kPa) from week 8 to 12. Radiotherapy slowed tumor progression. MRE is promising for the assessment of key glioma characteristics. NA TECHNICAL EFFICACY: Stage 2.

Can Automated 3-Dimensional Dixon-Based Methods Be Used in Patients With Liver Iron Overload?

Accurate quantification of liver iron concentration (LIC) can be achieved via magnetic resonance imaging (MRI). Maps of liver T2*/R2* are provided by commercially available, vendor-provided, 3-dimensional (3D) multiecho Dixon sequences and allow automated, inline postprocessing, which removes the need for manual curve fitting associated with conventional 2-dimensional (2D) gradient echo (GRE)-based postprocessing. The main goal of our study was to investigate the relationship among LIC estimates generated by 3D multiecho Dixon sequence to values generated by 2D GRE-based R2* relaxometry as the reference standard. A retrospective review of patients who had undergone MRI scans for estimation of LIC with conventional T2* relaxometry and 3D multiecho Dixon sequences was performed. A 1.5 T scanner was used to acquire the magnetic resonance studies. Acquisition of standard multislice multiecho T2*-based sequences was performed, and R2* values with corresponding LIC were estimated. The comparison between R2* and corresponding LIC estimates obtained by the 2 methods was analyzed via the correlation coefficients and Bland-Altman difference plots. This study included 104 patients (51 male and 53 female patients) with 158 MRI scans. The mean age of the patients at the time of scan was 15.2 (SD, 8.8) years. There was a very strong correlation between the 2 LIC estimation methods for LIC values up to 3.2 mg/g (LIC quantitative multiecho Dixon [qDixon; from region of interest R2*] vs LIC GRE [in-house]: r = 0.83, P < 0.01; LIC qDixon [from segmentation volume R2*] vs LIC GRE [in-house]: r = 0.92, P < 0.01); and very weak correlation between the 2 methods at liver iron levels >7 mg/g. Three-dimensional-based multiecho Dixon technique can accurately measure LIC up to 7 mg/g and has the potential to replace 2D GRE-based relaxometry methods.

Prognostic value of multiparametric cardiac magnetic resonance in sickle cell patients.

The aim of this multicenter study was to prospectively assess the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in sickle cell disease (SCD) patients. Among all patients with hemoglobinopathies consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network, we selected 102 SCD patients (34.38 ± 12.67years, 49 females). Myocardial iron overload (MIO) was measured by the multislice multiecho T2* technique. Atrial dimensions and biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect focal myocardial fibrosis. At baseline CMR, only two patients had significant MIO (global heart T2* < 20ms). During a mean follow-up of 63.01 ± 24.95months, 11 cardiovascular events (10.8%) were registered: 3 pulmonary hypertension, 2 supraventricular arrhythmias, 1 heart failure, 1 death for heart failure, 1 pulmonary embolism, 1 peripheral vascular disease, 1 transient ischemic attack, and 1 death after acute chest syndrome. In the multivariate analysis, the independent CMR predictors of cardiovascular events were left ventricular (LV) ejection fraction (hazard ratio-HR = 0.88; p = 0.025) and right ventricular (RV) mass index (HR = 1.09; p = 0.047). According to the receiver-operating characteristic curve analysis for adverse events, an LV ejection fraction < 58.9% and an RV mass index > 31g/m2 were optimal cut-off values. Reduced left ventricular ejection fraction and increased right ventricular mass index showed a significant prognostic value in patients with SCD. Our data seem to suggest that CMR may be added as a screening tool for identifying SCD patients at high risk for cardiopulmonary and vascular diseases.

P.32 Impact of age on muscle volume and T2-relaxation time during adulthood in mice using quantitative MRI

Overall ageing is associated with a loss of muscle volume and function over time; nevertheless, detailed changes of muscle tissue are incompletely understood. In this preliminary study, magnetic resonance imaging (MRI) was used to assess the effect of age on muscle volume and T2. A cohort of 13 C57Bl/6J Rj male mice was followed from 2.5 to 17 months of age. MRI acquisitions were done at 7 Tesla using a 1H surface cryoprobe. Muscle volume and T2 of the anterior compartment (TA+EDL: tibialis anterior + extensor digitorum longus) were assessed by cross sectional area (CSA) from high-resolution gradient-echo axial images and from a multi-slice multi echo MRI sequence, respectively. Student's paired t test and ANOVA were used for statistical analysis (p < 0.05). Body weight increased up to 12 months and stayed constant until 17 months of age. Muscle volume reached its maximum at 9 months of age. The maximum CSA of TA+EDL muscles, measured on a single slice, decreased significantly from 9 to 17 months of age (8±0.5 mm² at 9 m/o vs 7.1±0.4 mm² at 17 m/o). In parallel, muscle T2 increased significantly from 2.5 to 17 months of age (T2 at 2.5 m/o = 21.5 ±0.2 ms vs T2 at 17 m/o = 22.6±0.3 ms) and from 2.5 to 6 months of age (T2 at 6 m/o = 22.3±0.4 ms). A similar tendency was also observed between 9 and 17 months of age (T2 at 9 m/o = 22± 0.5; p = 0.054). Repeated acquisitions of high-resolution images allowed for longitudinal follow-up of muscle volume from 2.5 up to 17 months of age in mice. The onset of muscle ageing seems to be around 9 months whereas body weight still increases up to 12 months. Muscle T2 increased significantly with age over the timespan of the study. In young ages (2.5 to 6 m/o), T2 increase probably reflects slight changes of histological water compartmentation related to tissue maturation. Ongoing experiments will refine this longitudinal follow-up and provide data at older ages.

Gender Differences in the Development of CMR Abnormalities and Cardiac Complications: A Multicentric Prospective Study in a Cohort of Sickle Cell Disease Patients

Introduction. No data are available in literature about the relationship between gender and the development of CMR abnormalities and/or cardiac complications in sickle cell disease (SCD). This prospective and multicentre study aimed to assess if there was an association between gender and risk of cardiac iron overload, heart dilation, hypertrophy, and dysfunction, and myocardial fibrosis, assessed by Cardiovascular Magnetic Resonance (CMR), and of cardio-vascular complications in sickle cell disease (SCD) patients.Methods. We considered 115 SCD patients (58 females, 34.79±13.26 years), consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. Myocardial iron overload was assessed by the multislice multiecho T2* technique. Biventricular function parameters and atrial areas were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis.Results. Table 1 shows the comparison between sexes in the development of cardiac outcomes.Males and fameles showed a similar risk of accumulating cardiac iron, but both patients with cardiac iron were females.Compared to females, males showed a significant lower risk of developing biventricular hypertrophy (Kaplan-Meyer curve shown in Figure 1), although having a similar risk for biventricular dilation and dysfunction and for myocardial fibrosis. No patients with less than 34 years developed biventricular hypertrophy and age at the CMR was significantly higher in patients with hypertrophy versus patients without it (42.93±7.23 years versus 34.64±12.79 years; P=0.001).We recorded 12 (10.4%) cardiac events: 4 ischemic strokes, 5 arrhythmias (4 supraventricular and 1 ventricular), two pulmonary hypertensions and one pulmonary embolism. No prospective association was detected between gender and cardiac complications.Conclusion. In SCD male and female seem to show a comparable risk in developing cardiac complication, although compared to females, males showed a significant lower risk of developing biventricular hypertrophy. There are no specific guidelines for SCD patients and, as a consequence, the cardiovascular follow-up is conformed to that one of thalassemia patients (complete cardiac evaluation performed annually for both genders). Our data not support a different follow up time based on the gender. [Display omitted] DisclosuresPepe:Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.

Identifying trajectories of T2 relaxation time over age in the medial tibiofemoral cartilage in participants with pre-radiographic knee osteoarthritis

Identifying trajectories of T2 relaxation time over age in the medial tibiofemoral cartilage in participants with pre-radiographic knee osteoarthritis

Abstract 2770: Imaging cancer immunology: Monitoring CD47 mAb treatment in vivo by magnetic particle imaging

Abstract Introduction: The rapid growth of research into immuno-oncology research has fueled a need to be able to evaluate the efficacy of immunotherapies in a timely and comprehensive fashion. However, established non-invasive imaging approaches have been insufficient to meet all requirements. Magnetic Particle Imaging (MPI) is a novel tomographic molecular imaging technique that can be used to track iron-oxide in 3D in vivo, with sensitivity and specificity similar to nuclear medicine but without the complex workflow, safety, and half-life limitations. Methods: A murine breast tumor model was established by injecting 3 × 105 4T1 cells into the 4th mammary fat pad of 8-10 week female Blab/c mice. A CD47 monoclonal antibody (mAb) treatment was initiated by intraperitoneal injection of CD47 mAb (Bio-X Cell) at day 6 after tumor implantation. The treated and the control groups were then injected with an iron-oxide MPI tracer (6mg/kg) and then 3D MPI images were acquired 8, 11, 14 and 17 days after implantation. µCT and MRI were also acquired with a T2-weighted multi-slice, multi-echo (MSME) sequences at above time points. Both MPI and MRI images were co-registered and quantified. Tumors, liver, spleen and draining lymph nodes were then harvested, imaged, fixed, and stained with Perls Prussian blue. Results: Superparamagnetic iron oxide nanoparticles accumulation has been shown qualitatively to increase following CD47 mAb treatment [1]. To determine iron accumulation within the tumor, MPI was co-registered to both MRI µCT for anatomical context. All mice showed an accumulation of nanoparticles in the tumor and liver following injection in both MRI and MPI. Quantitation of iron at the tumor was performed and compared between the CD47-treated and untreated groups at every imaging time point with MPI. CD47 mAb treated breast tumors demonstrated enhanced positive contrast on 3D MPI images while a shortened T2 relaxation on MRI images. Iron content within the tumor was confirmed by ex vivo scanning followed by staining. Conclusions: By combining the sensitivity, specificity and quantitation potentials of MPI, information can be obtained on a preclinical model that monitors the efficacy of CD47 mAb cancer immunotherapy. With the high spatial resolution provided by MRI, coregistered MRI-MPI can be utilized to evaluate the response of tumor-associated macrophages to CD47 mAb and other cancer immunotherapies.

Application of high field magnetic resonance microimaging in polymer gel dosimetry

PurposeThe purpose of this work was to examine the suitability of VIPARnd polymer gel–9.4 T magnetic resonance microimaging system for high spatial resolution dose distribution measurements.MethodsThe VIPARnd samples (3 cm in outside diameter and 12 cm in height) were exposed to ionizing radiation by using a linear accelerator (Varian TrueBeam, USA; 6 MV x‐ray beam). In the calibration stage, nine gel dosimeter vials were irradiated in a water phantom homogenously to the doses from 1.5 to 30 Gy in order to obtain R2‒dose relation. In the verification stage, two gel dosimeter vials were irradiated in the half beam penumbra area of 10 × 10 cm radiation field using the amount of monitor units appropriate to deliver 20 Gy at the field center. The gels were imaged on a vertical 9.4 T magnetic resonance (MR) microimaging scanner using single slice and multislice (9 slices) multiecho (90 × 7 ms) sequences at the spatial resolutions of 0.2–0.4 × 0.2–0.4 × 3 mm3 and 0.2–0.4 × 0.2–0.4 × 1 mm3 respectively. The gels were subjected to microimaging during the period of two weeks after irradiation. The reference data consisted of the dose profiles measured using the diode dosimetry, radiochromic film, ionization chamber, and the water phantom system.ResultsThe VIPARnd‒9.4 T MR microimaging system was characterized by the dose sensitivity of 0.067 ± 0.002 Gy−1 s−1 at day 3 after irradiation. The dose resolution at 10 Gy (at P = 95%) was equal to 0.42 Gy at day 3 after irradiation using a single slice sequence (0.2 × 0.2 × 3 mm3) and 2.0 Gy at day 4 after irradiation using a multislice sequence (0.2 × 0.2 × 1 mm3) for one signal acquisition (measurement time: 15 min). These values were improved by ~1.4‐fold when using four signal acquisitions in the single slice sequence, and by ~2.78‐fold for 12 signal acquisitions in the multislice sequence. Furthermore, decreasing the in‐plane resolution from 0.2 × 0.2 mm2 to 0.4 × 0.4 mm2 resulted in a dose resolution of 0.3 Gy and 1 Gy at 10 Gy (at P = 95%) for one signal acquisition in the single slice and multislice sequences respectively (measurement time: 7.5 min).As reveals from the gamma index analysis the dose distributions measured at days 3–4 postirradiation using both VIPARnd verification phantoms agree with the data obtained using a silicon diode, assuming 1 mm/5% criterion. A good interphantom reproducibility of the polymer gel dosimetry was proved by monitoring of two phantoms up to 10 days after irradiation. However, the agreement between the dose distributions measured using the diode and polymer gel started to get worse from day 5 after irradiation.ConclusionThe VIPARnd–9.4T MR microimaging system allows to obtain dose resolution of 0.42 Gy at 10 Gy (at P = 95%) for a spatial resolution of 0.2 × 0.2 × 3 mm3 (acquisition time: 15 min). Further studies are required to improve a temporal stability of the gel‐derived dose distribution.

CMR for myocardial iron overload quantification: calibration curve from the MIOT Network.

R2* cardiac magnetic resonance (CMR) allows the non-invasive measurement of myocardial iron. We calibrated cardiac R2* values against myocardial tissue-measured iron concentration by using a segmental approach and we assessed the iron distribution. Five hearts of thalassemia patients were donated after death/transplantation to the CoreLab of the Myocardial Iron Overload in Thalassemia Network. A multislice multiecho R2* approach was adopted. After CMR, used as guidance, the heart was cut in three short-axis slices and each slice was cut into different equiangular segments according to AHA segmentation and differentiated into endocardial and epicardial layers. Tissue iron concentration was measured by atomic absorption spectrometer technique. Fifty-five samples were used since only for two hearts all the 16 samples were analyzed. Mean iron concentration was 4.71 ± 4.67mg/g dw. Segmental iron levels ranged from 0.24 to 13.78mg/g dw. The coefficient of variability of iron for myocardial segments ranged from 8.08 to 24.54% (mean 13.49 ± 6.93%). Iron concentration was significantly higher in the epicardial than in the endocardial layer (5.99 ± 6.01 vs 4.84 ± 4.87mg/g dw; p = 0.042). Four different circumferential regions (anterior, septal, inferior, and lateral) were defined. A circumferential heterogeneity was noted, with more iron in the anterior region, followed by the inferior region. The direct nonlinear fitting of R2* and [Fe] data led to the calibration curve: [Fe] = 0.0022 ∙ (R2*-ROI)1.462 (R-square = 0.956). Our data further validate R2* CMR using a segmental approach as a sensitive and early technique for quantifying iron distribution in the current clinical practice. • Calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration was provided. • A circumferential heterogeneity in cardiac iron distribution was detected: more iron was observed in the anterior region, followed by the inferior region. This finding corroborates the use of a segmental T2* CMR approach in the clinical practice to detect a heterogeneous iron distribution. • The comparison between the cardiac T2* values obtained with the region-based and the pixel-wise approaches showed a significant correlation and no significant difference but, in presence of significant iron load, the region-based approach resulted in significantly higher T2* values.

Prediction of Cardiac Complications in SCD

Introduction: Cardiac magnetic resonance (CMR) is the non-invasive gold standard for the quantification of biventricular functional parameters and for myocardial tissue characterization. The aim of this study was to prospectively assess the predictive value of CMR parameters for cardiovascular complications in sickle cell disease (SCD) patients. Methods: We considered 102 white SCD patients (34.38±12.67 years, 53 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Myocardial iron overload (MIO) was measured by the multislice multiecho T2* technique. Atrial dimensions and biventricular function parameters were quantified by cine images. Results: At baseline CMR only two patients had MIO (global heart T2*&lt;20 ms). During a mean follow-up was of 63.29±24.41 months, 10 cardiac events (9.8%) were registered: 3 pulmonary hypertension, 1 pulmonary embolism, 1 peripheral vascular disease, 1 transient ischemic attack, 2 supraventricular arrhythmias, 1 heart failure, and 1 death after acute chest syndrome. CMR predictors of cardiovascular events at univariate analysis were left ventricular ejection fraction and right ventricular mass index (see Table). Both variables remained independent predictors at multivariate analysis (see Table). Conclusions: Reduced left ventricular ejection fraction and increased right ventricular mass index showed a significant prognostic value in patients with SCD. Our data seem to suggest that also CMR could be added as screening tool for identifying SCD patients at high risk for pulmonary and systemic vasculopathy and death. Table Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

4326Reduction of cardiac outcomes in thalassemia major thanks to a ten-year national Italian networking

Abstract Introduction The MIOT (Myocardial Iron Overload in Thalassemia) Network was a network of thalassemia and CMR centers built in 2006 in order to assure homogeneous and standardized cardiac iron overload assessment for a significant number of patients. Purpose We describe the impact of this ten-year Network on cardiac iron, complications and deaths in patients with thalassemia major (TM). Methods 1746 TM patients (911 F; age 31.17±9.09 yrs) were enrolled in the MIOT Network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Results 1392 TM patients performed an end-of-study CMR. At the last CMR significantly higher global heart T2* values (35.44±10.69 ms vs 29.16±12.02 ms; P&lt;0.0001) and a significant lower number of patients with global heart T2*&lt;20 ms (26.3% vs 12.0%; P&lt;0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*&lt;20 ms, and homogeneous MIO (all T2*&lt;20 ms). At the last CMR a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were found (Figure 1). In patients with global heart T2*&lt;20 ms a significant increase in left ventricular ejection fraction (EF) (difference: 3.2±8.5%, P&lt;0.0001) as well as in right ventricular EF (difference: 1.2±8.9%, P=0.002) were detected. Based on CMR results the 75% of the patients changed the chelation therapy. At the last CMR the percentage of patients with an excellent/good compliance was significantly higher (94.8% vs 92.2%%; P&lt;0.0001). The complete history of cardiac complications-CC (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, peripheral vascular disease) was present for 1062 patients. Out of the 1001 patients with resolved CC or without CC before the enrolment in the project, the 6.6% had a CC before the enrolment in the project. During the study, the frequency of CC was 4.4%, significantly lower (P=0.023). In particular, the frequency of heart failure (HF) was significantly lower (3.5% vs 0.8%, P&lt;0.0001). Forty-six patients died during the study. HF continues to be the leading cause of death (30.4% of all causes), but there was a consistent decline in HF mortality rate, that was 60.2% in an Italian study dated 2004. No patients died for arrhythmias while cancer was the second leading cause of death. Conclusion Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. So, a national networking was effective in improving the care and reducing cardiac outcomes of TM patients.

A systematic optimization of 19F MR image acquisition to detect macrophage invasion into an ECM hydrogel implanted in the stroke-damaged brain

19F-MR imaging of perfluorocarbon (PFC)-labeled macrophages can provide a unique insight into their participation and spatio-temporal dynamics of inflammatory events, such as the biodegradation of an extracellular matrix (ECM) hydrogel implanted into a stroke cavity. To determine the most efficient acquisition strategy for 19F-MR imaging, five commonly used sequences were optimized using a design of experiment (DoE) approach and compared based on their signal-to-noise ratio (SNR). The fast imaging with steady-state precession (FISP) sequence produced the most efficient detection of a 19F signal followed by the rapid acquisition with relaxation enhancement (RARE) sequence. The multi-slice multi-echo (MSME), fast low angle shot (FLASH), and zero echo time (ZTE) sequences were significantly less efficient. Imaging parameters (matrix/voxel size; slice thickness, number of averages) determined the accuracy (i.e. trueness and precision) of object identification by reducing partial volume effects, as determined by analysis of the point spread function (PSF). A 96 × 96 matrix size (0.35 mm3) produced the lowest limit of detection (LOD) for RARE (2.85 mM PFPE; 119 mM 19F) and FISP (0.43 mM PFPE; 18.1 mM 19F), with an SNR of 2 as the detection threshold. Imaging of a brain phantom with PFC-labeled macrophages invading an ECM hydrogel further illustrated the impact of these parameter changes. The systematic optimization of sequence and imaging parameters provides the framework for an accurate visualization of 19F-labeled macrophage distribution and density in the brain. This will enhance our understanding of the contribution of periphery-derived macrophages in bioscaffold degradation and its role in brain tissue regeneration.

PS1295 IRON IN THE HUMAN HEARTS: DISTRIBUTION AND ASSOCIATION WITH R2∗ VALUES BY CMR

Background:T2∗ (or R2∗ = 1000/T2∗) cardiac magnetic resonance (CMR) allows the non‐invasive and reproducible measurement of myocardial iron and has been established as fundamental to the best practice management of iron loaded patients to improve morbidity and mortality.Aims:In the present study we calibrated cardiac R2∗ values against myocardial tissue ‐measured iron concentration by using a segmental approach and we assessed the distribution and regional variations in iron distribution.Methods:Five hearts of patients with thalassemia were donated after death (N = 4) or cardiac transplantation (N = 1) to the CoreLab of the MIOT (Myocardial Iron Overload in Thalassemia) Network. A multislice multiecho T2∗ approach was adopted. After CMR, used as guidance, the heart was cut in three short‐axis slice and each slice was cut into different equiangular segments accordingly with AHA segmentation and differentiated into endocardial and epicardial layer, the same ones in which the T2∗ was assessed. Tissue iron concentration in the segments was measured with an atomic absorption spectrometer.Results:55 samples were used since it was possible to analyze all the 16 samples only from two hearts due to medical‐forensic reasons. The mean iron concentration in all samples was 4.71 ± 4.67 mg/g dw. Segmental iron levels ranged from 0.24 to 13.78 mg/g dw. Mean iron concentration was significantly higher in the epicardial than in the endocardial layer (5.99 ± 6.01 mg/g dw vs 4.84 ± 4.87 mg/g dw; P = 0.042).The coefficient of variability (CoV) of iron for myocardial segments ranged from 8.08% to 24.54%, with a mean value for all patients of 13.49 ± 6.93%. Four different main circumferential regions (anterior, septal, inferior and lateral) were defined. A circumferential heterogeneity was noted, with more iron observed in the anterior region, followed by the inferior region. The heterogeneity in circumferential iron concentration expressed as percentage deviation of the regions from the global value is shown in the Figure 1A.A strong linear correlation (R‐square = 0.956) was found by plotting ln(R2∗‐ROI) and ln[Fe] with a slope s = 0.654 (95% confidence intervals‐CI = 0.616–0.693) and intercept i = 4.216 (95% CI = 4.150–4.281) (Figure 1B). The linear relation was converted to the calibration curve: [Fe] = 0.001591 X (R2∗)1.529.Summary/Conclusion:Our data suggests an heterogeneous pattern of cardiac iron distribution with higher epicardial layer involvement. Heart R2∗ provided a robust calibration against chemically assayed cardiac iron, further validating the current clinical practice of monitoring cardiac iron in vivo by CMR.image

Comprehensive description of T2 value spatial variations in non-osteoarthritic femoral cartilage using three-dimensional registration of morphological and relaxometry data

PurposeThe aim of this study was to develop and assess a method of quantifying cartilage T2 relaxation times in a series of volumes of interest (VOIs) covering the entire cartilage of the femoral condyles. Subsequently, the method was used to test for T2 spatial variations in non-osteoarthritic (OA) knees. MethodsTen non-OA subjects (five female, average 30 years) were enrolled after informed consent. Three-dimensional bone and cartilage models were created by double echo steady state (DESS) morphological magnetic resonance image (MRI) segmentation, and the models were semi-manually registered with multi-slice, multi-echo (MSME) T2 MRI. Mean T2 values were calculated for 12 VOIs derived from cartilage thickness literature and their respective superficial and deep layers. ResultsAnalyses showed that intra- and inter-rater reliabilities of the presented method were “good” to “excellent” in more than 90% of the VOIs. Additionally, several spatial differences in T2 values were observed, including, for the medial condyle, higher T2 values in the anterior and central VOIs versus in the posterior VOI (p < .05). T2 values were also generally higher in the superficial versus deep layers (p < .05). ConclusionsThe presented MRI T2 analysis method is reliable and provides a comprehensive quantification of spatial heterogeneity of healthy cartilage compositional properties. This method can be further applied to better understand knee OA pathophysiology and potentially define clinically relevant diagnostic features of the disease.

Genotypic Groups As Risk Factor for Cardiac MR Abnormalities and Complications in Thalassemia Major

Introduction. Beta thalassemia major (β-TM) displays a great deal of genotypic heterogeneity, not fully investigated in terms of cause-effect. This prospective and multicentre study aimed to detect if different genotypic groups could predict the development of cardiovascular magnetic resonance (CMR) abnormalities and cardiac complications (CC).Methods. We considered 708 β-TM patients (373 females, 30.05±9.47 years), consecutively enrolled in Myocardial Iron Overload in Thalassemia (MIOT) network. Data were collected from birth to the first CMR imaging scan. Myocardial iron overload was assessed by the multislice multiecho T2* technique. Biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis.Results. On the basis of the type of gene mutation, three groups of patients were identified: homozygotes β+ (N=158), compound heterozygotes β+ / β° (N=298) and homozygotes β° (N=252). Table 1 shows the effect of genotype group on the development of different cardiac outcomes. Compared to the milder genotype group homozygotes β+, the other two groups showed a significantly higher risk of myocardial iron overload (MIO) and left ventricular dysfunction. We recorded 90 (13.0 %) cardiac events: 46 heart failures (HF), 38 arrhythmias (33 supraventricular, 3 ventricular and 2 hypoinetic) and 6 pulmonary hypertensions (PH). No prospective association was detected between genotype group and HF and PH. The homozygous β° group showed a significantly higher risk of arrhythmias than the homozygous β+ group and at the limit of significance than the compound heterozygotes. Globally, homozygotes β° showed a significantly higher risk of CC than homozygotes β+.Conclusion. Different genotypic groups predict the development of MIO, left ventricular dysfunction, arrhythmias and CC in β-TM patients. These data support the knowledge of the different genotypic groups in the clinical management of β-TM patients. [Display omitted] DisclosuresPepe:Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Impact of a Ten-Year National Italian Networking on Cardiac Complications in Patients with Thalassemia Major

▪Introduction. The MIOT (Myocardial Iron Overload in Thalassemia) Network was a national Italian network constituted by thalassemia and magnetic resonance imaging (MRI) centers built in 2006. The main aim was to assure available, accessible homogeneous and standardized T2* MRI cardiac and liver iron overload assessments for a significant number of patients with emoglobinopathies. Moreover, the creation of a solid clinical-instrumental web based database allowed data exchange between centers and constituted a means of monitoring health care processes and outcomes. We describe the impact of this ten-year Network on cardiac complications in patients with thalassemia major (TM).Methods. Among the 2497 emoglobinopathies patients consecutively enrolled in the MIOT Network we considered the 1401 TM patients who performed an end-of-study MRI. Per protocol the MRI follow up was scheduled every 18±3 months. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images.Results. At the last MRI significantly higher global heart T2* values (35.5±10.7 ms vs 29.2±12.0 ms; P<0.0001) and a significant lower number of patients with global heart T2*<20 ms (26.3% vs 12.0%; P<0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*<20 ms, and homogeneous MIO (all segments with T2*<20 ms). Figure 1 shows the frequency of the 4 patterns at both scans. At the last MRI a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were detected. An improvement in MIO, that is a transition to a better risk class, was detected in the 68.4% of patients showing MIO at the baseline (at least one pathologic segment).In patients with significant baseline MIO (global heart T2*<20 ms) a significant increase in left ventricular ejection fraction (EF) (mean difference: 3.2±8.5 %, P<0.0001) as well as in right ventricular EF (mean difference: 1.2±8.9 %, P=0.002) were detected with a concordant improvement of MIO status.Based on MRI results the 75% of the patients changed the chelation therapy. At the last MRI the percentage of patients with an excellent/good compliance was significantly higher (94.7% vs 92.7%%; P=0.034).The 13.1% of the patients had a cardiac complication (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, and peripheral vascular disease) before the enrolment in the project. During the study, the frequency of cardiac complications was 7.9 %, significantly lower (P<0.0001). In particular, the frequency of heart failure was significantly lower (5.9% vs 1.7%, P<0.0001).Conclusion. Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients and a consequent improvement of cardiac function and reduction of heart failure. So, a national networking as the MIOT project was effective in improving the care and reducing cardiac outcomes of TM patients. [Display omitted] DisclosuresPepe:Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

A Hyperfluorinated Hydrophilic Molecule for Aqueous 19F MRI Contrast Media.

Fluorine-19 (19F) magnetic resonance imaging (MRI) has the potential for a wide range of in vivo applications but is limited by lack of flexibility in exogenous probe formulation. Most 19F MRI probes are composed of perfluorocarbons (PFCs) or perfluoropolyethers (PFPEs) with intrinsic properties which limit formulation options. Hydrophilic organofluorine molecules can provide more flexibility in formulation options. We report herein a hyperfluorinated hydrophilic organoflourine, ET1084, with ∼24 wt. % 19F content. It dissolves in water and aqueous buffers to give solutions with ≥8 M 19F. 19F MRI phantom studies at 9.4T employing a 10-minute multislice multiecho (MSME) scan sequence show a linear increase in signal-to-noise ratio (SNR) with increasing concentrations of the molecule and a detection limit of 5 mM. Preliminary cytotoxicity and genotoxicity assessments suggest it is safe at concentrations of up to 20 mM.

Effects of oxygen challenging to tissue redox and pO2 status

Nitroxide free radicals can serve as redox-sensitive MRI contrast agents useful to image the redox status of tissue of interest. In this study, the effect of oxygen content in the inspired gas on the kinetics of metabolism of three nitroxides has been evaluated in the muscle and tumor in mice.SCC tumors (approximate size of 1.0 cm3) on the right hind leg of female C3H/Hen MTV- mice were prepared. Three nitroxides, 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP), and 4-hydroxy-tetramethylpiperidine-N-oxyl (TEMPOL), having different lipophilicities were compared using MR redox imaging. T1-mapping of the tissues was obtained using a multi-slice multi-echo (MSME) sequence with several TRs.The three nitroxides showed differences in accumulation and metabolism/clearance in muscle and tumor. The cell impermeable nitroxide CxP displayed kinetic patterns of slow enhancement followed by a slow decline typical of clearance rather than metabolism. The cell permeable CmP on the other hand showed a relatively faster uptake and metabolism with a modestly higher rate of metabolism in the tumor than muscle. The TEMPOL on the other hand displayed a rapid uptake and reduction with a trend of significantly rapid decay rate in tumor tissue, while slightly higher maximum signal intensity and slower decay rate was observed in normal muscle. The reduction rate of TEMPOL in the tumor was significantly enhanced when the breathing gas had 100%-oxygen while it was not significantly different in the muscle. EPR oximetry studies monitoring the oxygen dependent linewidth of TEMPOL showed that the pO2 in the healthy tissue during carbogen breathing significantly increased normal tissue pO2 compared to air breathing whereas breathing 100%-oxygen made normal tissue slight hypoxic. Since TEMPOL is a radioprotector, our studies show that a combination of 100%-oxygen breathing and TEMPOL has a potential to enhance radioprotective effects to normal tissue.

Determination of oil and moisture distribution in fried potatoes using magnetic resonance imaging

AbstractThe objective of this study was to examine oil and moisture distribution in fried potatoes using Magnetic Resonance Imaging (MRI) as nondestructive technique and to establish a correlation between moisture content and oil content of fried potatoes with MRI results. In addition, it was aimed to evaluate the effects of frying time, predrying and precoating by hydroxyprophylmethylcellulose (HPMC) on moisture loss and oil uptake of the samples. Coating with HPMC was the best pretreatment to reduce oil uptake. Spin echo (SE) and multislice–multi‐echo (MSME) pulse sequences were used to obtain longitudinal relaxation time (T1) weighted and water suppression images and also spin–spin relaxation time (T2) maps of the samples. Results confirmed that by using different MR imaging sequences, prediction of oil and moisture contents (r &gt; 0.70) and exploring the distribution of oil and moisture within the fried pototaes was possible.Practical applicationsMRI, as being a nondestructive technique offers advantages compared to conventional methods of moisture and oil content measurements. Moreover, use of spin–spin relaxation time (T2) maps provided further information for moisture and oil distribution on the samples. MR images could also be used to extract information about the microstructure of the sample.

192 - Oxygen Induced Tissue Hypoxia

The effect of oxygenation challenges to the in vivo pharmacokinetics of nitroxyl contrast agents in squamous cell carcinoma (SCC) tumor tissue and normal muscle was investigated. In addition, difference of T1 relaxivity (ΔR1) in the normal muscle and the SCC tumor tissues were compared under several gas-challenging conditions. SCC tumor cells were injected into the right thighs of C3H/Hen MTV- female mice and allowed to grow for 9 days, which resulted in a tumor of approximate size of 0.7 cm3. Pharmacokinetic profiles of three nitroxyl contrast agents, 3-carboxy-2,2,5,5-tetramethyl-pyrrolidine-N-oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethyl-pyrrolidine-N-oxyl (CmP), and 4-hydroxy-tetramethylpiper-idine-N-oxyl (TPL), having different lipophilicities were compared using MR redox imaging. To perform T1 mapping, spin echo images were obtained using a multi-slice multi-echo (MSME) sequence with 5 TRs (repetition time: 4800, 3200, 1600, 800 and 400 ms). Exposure to 100% oxygen resulted in a rapid decay rate of TPL in tumor tissue, while no effect or slightly slower decay rate was observed in normal muscle. The 100% oxygen breathing also made distribution of nitroxyl probes into tissue lower. As a result, 100% oxygen breathing can make relatively large difference of TPL concentration between normal and tumor tissue. Carbogen and 1.5 atm hyperbaric oxygen (HBO) challenges could increase ΔR1 in the tissue, while 100% oxygen breathing decreased the ΔR1 in both the normal and the tumor tissue. The pO2 in the healthy muscle tissue during 100% oxygen breathing measured by the EPR method also showed lower or similar values compared to the air breathing. Pimonidazole staining confirmed that 100% oxygen breathing increased hypoxia in tumor tissue. A combination of 100% oxygen with TPL has a potential to enhance the radioprotection selectively in normal tissues.