Comparison of Three Ultrasmall, Superparamagnetic Iron Oxide Nanoparticles for MRI at 3.0 T.

BACKGROUND: The ultrasmall, superparamagnetic iron oxide (USPIO) nanoparticle ferumoxytol has unique applications in cardiac, vascular, and body magnetic resonance imaging (MRI) due to its long intravascular half-life and suitability as a blood pool agent. However, limited availability and high cost have hindered its clinical adoption. A new ferumoxytol generic, and the emergence of MoldayION as an alternative USPIO, represent opportunities to expand the use of USPIO-enhanced MRI techniques. PURPOSE: To compare in vitro and in vivo MRI relaxometry and enhancement of Feraheme, generic ferumoxytol, and MoldayION. STUDY TYPE: Prospective. ANIMAL MODEL: Ten healthy swine and six swine with artificially induced coronary narrowing underwent cardiac MRI. FIELD STRENGTH/SEQUENCE: 3.0 T; T1-weighted (4D-MUSIC, 3D-VIBE, 2D-MOLLI) and T2-weighted (2D-HASTE) sequences pre- and post-contrast. ASSESSMENT: We compared the MRI relaxometry of Feraheme, generic ferumoxytol, and MoldayION using saline, plasma, and whole blood MRI phantoms with contrast concentrations from 0.26 mM to 2.10 mM. In-vivo contrast effects on T1- and T2-weighted sequences and fractional intravascular contrast distribution volume in myocardium, liver, and spleen were evaluated. STATISTICAL TESTS: Analysis of variance and covariance were used for group comparisons. A P value <0.05 was considered statistically significant. RESULTS: The r1 relaxivities for Feraheme, generic ferumoxytol, and MoldayION in saline (22 °C) were 7.11 ± 0.13 mM-1  s-1 , 8.30 ± 0.29 mM-1  s-1 , 8.62 ± 0.16 mM-1  s-1 , and the r2 relaxivities were 111.74 ± 3.76 mM-1  s-1 , 105.07 ± 2.20 mM-1  s-1 , and 109.68 ± 2.56 mM-1  s-1 , respectively. The relationship between contrast concentration and longitudinal (R1) and transverse (R2) relaxation rate was highly linear in saline and plasma. The three agents produced similar in vivo contrast effects on T1 and T2 relaxation time-weighted sequences. DATA CONCLUSION: Relative to clinically approved ferumoxytol formulations, MoldayION demonstrates minor differences in in vitro relaxometry and comparable in vivo MRI characteristics. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Arterial spin labeling magnetic resonance imaging quantifies tissue perfusion around foot ulcers.

Objective: Tools that quantify tissue perfusion of the foot are deficient, contributing to the uncertainty in predicting ulcer healing potential. This pilot study aims to quantify peri-wound foot perfusion at various tissue depths using a novel application of pseudo-continuous arterial spin labeling magnetic resonance imaging. Methods: Ten diabetic patients with neuropathic wounds and 20 healthy volunteers without wounds were recruited. Wounds were graded according to the Wound, Ischemia, Foot Infection (WIfI) system. All subjects underwent a noncontrasted ASL MRI of the foot for perfusion measurements. For healthy volunteers, perfusion was compared at rest and during sustained toe flexion between four regions: lateral plantar, medial plantar, lateral calcaneal, and medial calcaneal. Evaluations of diabetic volunteers compared perfusion between four zones: wound, near border, far border, and remote. Remote zone perfusion in diabetics was compared with perfusion in the plantar foot of healthy volunteers. Results: There were 11 wounds, which were located over the metatarsal heads in five, the stump of a transmetatarsal amputation in three, the heel in two, and the mid foot in one. The median WIfI stage was 2. One patient had a WIfI ischemia grade of 1; the remaining patients' grades were 0. The mean ankle-brachial index was 1.0 ± 0.3. There were two patients with a WIfI foot infection grade of 1; the remaining patients' grades were 0. In healthy volunteers, plantar foot perfusion with sustained toe flexion was 43.9 ± 1.7 mL/100g/min and significantly higher than perfusion at rest (27.3 ± 2.7 mL/100g/min; P < .001). In diabetic patients, perfusion at the wound, near border, far border, and remote regions was 96.1 ± 10.7, 92.7 ± 9.4, 73.4 ± 8.2, and 62.8 ± 2.7 mL/100g/min. Although this perfusion pattern persisted throughout the depth of the wound, perfusion decreased with tissue depth. In the near border, perfusion at 20% of the wound depth was 124.0 ± 35.6 mL/100g/min and 69.9 ± 10.1 mL/100g/min at 100% (P = .006). Lastly, remote perfusion in diabetics was 2.3 times the plantar perfusion in healthy volunteers (27.3 ± 2.7 mL/100g/min; P < .001). Conclusions: The pattern of resting tissue perfusion around nonischemic diabetic foot ulcers was successfully quantified with arterial spin labeling magnetic resonance imaging. Diabetic patients with wounds were hyperemic compared with healthy volunteers. There was a 1.5-fold increase in peri-wound tissue perfusion relative to the rest of the foot. This study is the first step in developing a tool to assess the perfusion deficit in ischemic wounds.

Ferumoxytol-enhanced 4D multiphase, steady-state imaging with magnetic resonance in congenital heart disease: ventricular volume and function across 2D and 3D software platforms.

Background: Quantitative ventricular volumetry and function are important in the management of congenital heart disease (CHD). Ferumoxytol-enhanced (FE) 4D multiphase, steady state imaging with contrast enhancement (MUSIC) enables high-resolution, 3D cardiac phase-resolved magnetic resonance imaging (MRI) of the beating heart and extracardiac vessels in a single acquisition and without concerns about renal impairment. We aim to evaluate the semi-automatic quantification of ventricular volumetry and function of 4D MUSIC MRI using 2D and 3D software platforms. Methods: This HIPAA-compliant and IRB-approved study prospectively recruited 50 children with CHD (3 days to 18 years) who underwent 4D MUSIC MRI at 3.0T between 2013-2017 for clinical indications. Each patient was either intubated in the neonatal intensive care unit (NICU) or underwent general anesthesia at MRI suite. For 2D analysis, we reformatted MUSIC images in Digital Imaging and Communications in Medicine (DICOM) format into ventricular short-axis slices with zero interslice gap. For 3D analysis, we imported DICOMs into a commercially available 3D software platform. Using semi-automatic thresholding, we quantified biventricular volume and ejection fraction (EF). We assessed the bias between MUSIC-derived 2D vs. 3D measurements and correlation between MUSIC vs. conventional 2D balanced steady-state free precession (bSSFP) cine images. We evaluated intra- and inter-observer agreement. Results: There was a high degree of correlation between MUSIC-derived volumetric and functional measurements using 2D vs. 3D software (r=0.99, P<0.001). Volumes derived using 3D software platforms were larger than 2D by 0.2 to 2.0 mL/m2 whereas EF measurements were higher by 1.2-3.0%. MUSIC volumetric and functional measures derived from 2D and 3D software platforms corresponded highly with those derived from multi-slice SSFP cine images (r=0.99, P<0.001). The mean difference in volume for reformatted 4D MUSIC relative to bSSFP cine was 1.5 to 3.9 mL/m2. Intra- and inter-observer reliability was excellent. Conclusions: Accurate and reliable ventricular volumetry and function can be derived from FE 4D MUSIC MRI studies using commercially available 2D and 3D software platforms. If fully validated in multicenter studies, the FE 4D-MUSIC pulse sequence may supercede conventional multislice 2D cine cardiovascular MRI acquisition protocols for functional evaluation of children with complex CHD.

Steady-state ferumoxytol-enhanced MRI: early observations in benign abdominal organ masses and clinical implications.

INTRODUCTION: The off-label use of ferumoxytol as a vascular MR imaging agent is growing rapidly. However, the properties of ferumoxytol suggest that it may play an important role in the detection and characterization of abdominal mass lesions. METHODS: Thirty-six patients with benign abdominal mass lesions who underwent MR angiography with ferumoxytol also had T2-weighted HASTE imaging and fat-suppressed 3D T1-weighted imaging. The T1 and T2 enhancement characteristics of the lesions were analyzed and correlated with other imaging modalities and/or surgical findings and/or clinical follow-up. RESULTS: In all patients with benign masses in the liver (n = 22 patients), spleen (n = 6 patients), kidneys (n = 33 patients), adrenal (n = 2 patients) and pancreas (n = 4 patients), based on the enhancement characteristics with ferumoxytol, readers were confident of the benign nature of the lesions and their conclusions were consistent with correlative imaging, tissue sampling and follow-up. One patient with a suspicious enhancing 2F Bosniak renal cyst had renal cell carcinoma confirmed on biopsy. CONCLUSION: Ferumoxytol-enhanced MRI can increase diagnostic confidence for benign abdominal masses and can increase the conspicuity of mass lesions, relative to unenhanced MRI.

Three-Dimensional Congenital Heart Models Created With Free Software and a Desktop Printer: Assessment of Accuracy, Technical Aspects, and Clinical Use.

BACKGROUND: Three-dimensional printing is increasingly recognized as a valuable tool for congenital heart disease (CHD) procedural planning and education. Cost and complexity currently limit the more widespread adoption of this technology. We sought to demonstrate the accuracy of 3D printed CHD models created from contrast-enhanced magnetic resonance imaging (MRI) and computed tomography (CT) scans using free software and an inexpensive desktop fused filament fabrication (FFF) printer. METHODS: Solid segmentations of the intracardiac blood pool were created with the program ITK-SNAP. Using the computer program Meshmixer, the segmentation model was hollowed to create a 0.8 mm shell with the inner surface representing endocardium. Three-dimensional models were created on an FFF printer. Four arteries and a ventricular septal defect (VSD) were 3D printed and measured for accuracy. Five models were used to assess candidacy for biventricular surgical repair and one to guide an interventional catheterization. RESULTS: All six patients underwent intervention planned with the 3D models. The computer model shell walls all achieved specifications within 0.05 mm of the designated 0.8 mm thickness and the original solid blood pool segmentation fit within the hollowed 3D model. The 3D printed arteries and VSD all measured accurately to within 0.5 mm of their source computer model. CONCLUSION: Accurate 3D printed models of complex, pediatric CHD may be created from volumetric MRI and CT studies using free online software and printed on an inexpensive desktop printer.

Factors Associated with Symptomology of Celiac Artery Compression and Outcomes following Median Arcuate Ligament Release.

BACKGROUND: This study aims to identify potential risk factors for becoming symptomatic in patients with radiographic celiac artery compression (CAC) as well as prognostic factors for patients with median arcuate ligament syndrome (MALS) who underwent surgical ligament release. METHODS: This is a retrospective cohort study of patients with findings of CAC on computed tomography or magnetic resonance angiography (CT/MRA) who were asymptomatic and who were diagnosed with MALS at a single university hospital between January 2001 and 2018. RESULTS: Following a review of 1,330 CT/MRA reports, a total of 109 patients were identified as having radiographically apparent CAC. Among these, 48 (44.0%) patients were symptomatic. Univariate comparison between those with and without symptoms showed that symptomatic patients were more commonly younger than 30 years old [17/48 (35.4%) vs. 8/61 (13.1%), P = 0.006], had a history of prior abdominal surgery [25/48 (52.1%) vs. 18/61 (29.5%), P = 0.017], and had high-grade stenosis [32/43 (74.4%) vs. 25/61 (41.0%), P = 0.001]. Among 41 included patients who underwent surgical release of the median arcuate ligament including open, laparoscopic, and robotic approaches, 82.9% reported overall clinical improvement, 5/41 (12.2%) reported persistent pain, and 13/36 (36.0%) experienced pain recurrence. The only identified risk factor associated with symptom recurrence was American Society of Anesthesiologists class III [7/13 (53.8%) vs. 4/23 (17.4%), P = 0.029]. CONCLUSIONS: The severity of stenosis and prior abdominal surgery both contributed to symptom development in patients with radiographically apparent CAC from the median arcuate ligament.

Intermodality feature fusion combining unenhanced computed tomography and ferumoxytol-enhanced magnetic resonance angiography for patient-specific vascular mapping in renal impairment.

OBJECTIVE: The purpose of this study was to establish the feasibility of fusing complementary, high-contrast features from unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for preprocedural vascular mapping in patients with renal impairment. METHODS: In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, 15 consecutive patients underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multifeature image. Source images from CT and MRA were segmented and registered. To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on three-dimensional (3D) models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment. We then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points). Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal). The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets. The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent nonconcordance between the source FE-MRA and fused images. The offsets were compared using concordance correlation coefficients. Interobserver agreement was assessed using intraclass correlation coefficients and Bland-Altman analyses. RESULTS: Thirteen patients (aged 76 ± 12 years; seven female) with aortic valve stenosis and chronic kidney disease and two patients with thoracoabdominal vascular aneurysms and chronic kidney disease underwent FE-MRA for preprocedural vascular assessment, and unenhanced CT examinations were available in all patients. No ferumoxytol-related adverse events occurred. There were 247 matched POIs evaluated on the source FE-MRA and fused images. In patients with implantable medical devices, the mean offsets in spatial position were 0.31 ± 0.51 mm (ρ = 0.99; Cb = 1; 95% confidence interval [CI], 0.99-0.99) for Δx, 0.27 ± 0.69 mm (ρ = 0.99; Cb = 0.99; 95% CI, 0.99-0.99) for Δy, and 0.20 ± 0.59 mm (ρ = 1; Cb = 1; 95% CI, 0.99-1.00) for Δz. Interobserver agreement was excellent (intraclass correlation coefficient, >0.99). The mean difference in offset between readers was 1.5 mm. CONCLUSIONS: Accurate 3D feature fusion is feasible, combining luminal information from FE-MRA with vessel wall information on unenhanced CT. This framework holds promise for combining the complementary strengths of magnetic resonance imaging and CT to generate information-rich, multifeature composite vascular images while avoiding the respective risks and limitations of both modalities.

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI.

Background Ferumoxytol is approved for use in the treatment of iron deficiency anemia, but it can serve as an alternative to gadolinium-based contrast agents. On the basis of postmarketing surveillance data, the Food and Drug Administration issued a black box warning regarding the risks of rare but serious acute hypersensitivity reactions during fast high-dose injection (510 mg iron in 17 seconds) for therapeutic use. Whereas single-center safety data for diagnostic use have been positive, multicenter data are lacking. Purpose To report multicenter safety data for off-label diagnostic ferumoxytol use. Materials and Methods The multicenter ferumoxytol MRI registry was established as an open-label nonrandomized surveillance databank without industry involvement. Each center monitored all ferumoxytol administrations, classified adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1-5), and assessed the relationship of AEs to ferumoxytol administration. AEs related to or possibly related to ferumoxytol injection were considered adverse reactions. The core laboratory adjudicated the AEs and classified them with the American College of Radiology (ACR) classification. Analysis of variance was used to compare vital signs. Results Between January 2003 and October 2018, 3215 patients (median age, 58 years; range, 1 day to 96 years; 1897 male patients) received 4240 ferumoxytol injections for MRI. Ferumoxytol dose ranged from 1 to 11 mg per kilogram of body weight (≤510 mg iron; rate ≤45 mg iron/sec). There were no systematic changes in vital signs after ferumoxytol administration (P > .05). No severe, life-threatening, or fatal AEs occurred. Eighty-three (1.9%) of 4240 AEs were related or possibly related to ferumoxytol infusions (75 mild [1.8%], eight moderate [0.2%]). Thirty-one AEs were classified as allergiclike reactions using ACR criteria but were consistent with minor infusion reactions observed with parenteral iron. Conclusion Diagnostic ferumoxytol use was well tolerated, associated with no serious adverse events, and implicated in few adverse reactions. Registry results indicate a positive safety profile for ferumoxytol use in MRI. © RSNA, 2019 Online supplemental material is available for this article.

Intraesophageal aortopulmonary collateral artery occlusion in an infant with Tetralogy of Fallot and flow-dependent major aortopulmonary collateral arteries.

Patients with flow-dependent aortopulmonary collateral arteries often exhibit tenuous clinical statuses. Here we present an infant with Tetralogy of Fallot with pulmonary atresia (TOF-PA) and major aortopulmonary collateral arteries (MAPCAs) who experienced clinically significant oxygen desaturations during feedings. These frequent episodes were attributed to gastroesophageal reflux. In preparation for possible surgical correction of her complex congenital heart condition, she was intubated for a cardiac catheterization to better characterize her anatomy, but terminally decompensated shortly after extubation and restarting feeding. On autopsy, very mild evidence of esophageal reflux was present; instead, one of her four aortopulmonary collateral arteries was unexpectedly discovered traversing through the muscular layer of her esophageal wall. This finding was confirmed microscopically with significant intimal hyperplasia compared to uninvolved collateral arteries. The remainder of the autopsy findings, including her myocardium, lungs, and esophagus, were unremarkable. Given the feeding-associated oxygen desaturations present in life and the aberrant collateral artery's comparative stenosis at death, we speculate that the repetitive trauma of esophageal peristalsis was not only significant enough to temporarily impact oxygenation but, over time, led to near-occlusion of the intraesophageal collateral artery, which may have contributed to the terminal decompensation of this already tenuous patient.

4D MUSIC CMR: value-based imaging of neonates and infants with congenital heart disease.

BACKGROUND: 4D Multiphase Steady State Imaging with Contrast (MUSIC) acquires high-resolution volumetric images of the beating heart during uninterrupted ventilation. We aim to evaluate the diagnostic performance and clinical impact of 4D MUSIC in a cohort of neonates and infants with congenital heart disease (CHD). METHODS: Forty consecutive neonates and infants with CHD (age range 2 days to 2 years, weight 1 to 13 kg) underwent 3.0 T CMR with ferumoxytol enhancement (FE) at a single institution. Independently, two readers graded the diagnostic image quality of intra-cardiac structures and related vascular segments on FE-MUSIC and breath held FE-CMRA images using a four-point scale. Correlation of the CMR findings with surgery and other imaging modalities was performed in all patients. Clinical impact was evaluated in consensus with referring surgeons and cardiologists. One point was given for each of five key outcome measures: 1) change in overall management, 2) change in surgical approach, 3) reduction in the need for diagnostic catheterization, 4) improved assessment of risk-to-benefit for planned intervention and discussion with parents, 5) accurate pre-procedural roadmap. RESULTS: All FE-CMR studies were completed successfully, safely and without adverse events. On a four-point scale, the average FE-MUSIC image quality scores were >3.5 for intra-cardiac structures and >3.0 for coronary arteries. Intra-cardiac morphology and vascular anatomy were well visualized with good interobserver agreement (r = 0.46). Correspondence between the findings on MUSIC, surgery, correlative imaging and autopsy was excellent. The average clinical impact score was 4.2 ± 0.9. In five patients with discordant findings on echo/MUSIC (n = 5) and catheter angiography/MUSIC (n = 1), findings on FE-MUSIC were shown to be accurate at autopsy (n = 1) and surgery (n = 4). The decision to undertake biventricular vs univentricular repair was amended in 2 patients based on FE-MUSIC findings. Plans for surgical approaches which would have involved circulatory arrest were amended in two of 28 surgical cases. In all 28 cases requiring procedural intervention, FE-MUSIC provided accurate dynamic 3D roadmaps and more confident risk-to-benefit assessments for proposed interventions. CONCLUSIONS: FE-MUSIC CMR has high clinical impact by providing accurate, high quality, simple and safe dynamic 3D imaging of cardiac and vascular anatomy in neonates and infants with CHD. The findings influenced patient management in a positive manner.

Injection of gadolinium contrast through pediatric central venous catheters: a safety study.

BACKGROUND: Catheter rupture during CT angiography has prompted policies prohibiting the use of electronic injectors with peripherally inserted central venous catheters (PICCs) not only for CT but also for MRI. Consequently, many institutions mandate hand injection for MR angiography, limiting precision of infusion rates and durations of delivery. OBJECTIVE: To determine whether electronic injection of gadolinium-based contrast media through a range of small-caliber, single-lumen PICCs would be safe without risk of catheter rupture over the range of clinical protocols and determine whether programmed flow rates and volumes were realized when using PICCs for contrast delivery. MATERIALS AND METHODS: Experiments were performed and recorded using the Medrad Spectris Solaris EP MR Injection System. PICC sizes, contrast media and flow rates were based on common institutional protocols. RESULTS: No catheters were damaged during any experiments. Mean difference between programmed and delivered volume was 0.07 ± 0.10 mL for all experiments. Reduced flow rates and prolonged injection durations were observed when the injector's pressure-limiting algorithm was triggered, only in protocols outside the clinical range. CONCLUSION: PICCs commonly used in children can withstand in vitro power injection of gadolinium-based contrast media at protocols significantly above clinical levels.

Gender and iron genes may modify associations between brain iron and memory in healthy aging.

Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON+) vs noncarrier (IRON-) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON+ vs IRON- status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r=-0.50, p=0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRON- group (r=-0.49, p=0.005) but not in the IRON+ group. Between-group interactions (p=0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.

Preoperative magnetic resonance angiography detection of septocutaneous perforators in fibula free flap transfer.

OBJECTIVE: To investigate whether preoperative magnetic resonance angiography (MRA) is predictive of surgical findings in fibula free flap surgery for head and neck reconstruction. METHODS: Retrospective review (April 2004 until September 2009) of 123 patients who underwent preoperative MRA as part of surgical planning for fibula free flap tissue transfer for head and neck reconstruction. Each MRA was reviewed by a board-certified radiologist masked to the intraoperative findings and to the number of septocutaneous perforators documented. Operative notes were reviewed and the number of septocutaneous perforators found during the operation was recorded. A κ interrater agreement statistic was calculated to compare these values. RESULTS: Two vascular anomalies found during the operation were undetected by MRA. Analysis of the entire cohort demonstrated that agreement between the number of perforators documented on MRA and the number found intraoperatively approached zero (unweighted κ = -0.088, P = .04). The agreement between the 2 values was 17.9% and the average percentage correctly classified was 10.9%. CONCLUSIONS: Contrary to previous reports, preoperative MRA does not accurately predict the presence and/or number of skin perforators found intraoperatively for a fibula free flap operation. The surgeon should not be dissuaded from planning a fibula free flap operation if skin perforators appear unfavorable on preoperative MRA because intraoperative observation is definitive. The surgeon should prepare for anomalous cases in which perforators may arise from the posterior tibial system. Further investigation is needed to achieve more accurate imaging modalities for evaluating septocutaneous perforators prior to free fibula flap transfer.

Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men.

Prevalent gene variants involved in iron metabolism [hemochromatosis (HFE) H63D and transferrin C2 (TfC2)] have been associated with higher risk and earlier age at onset of Alzheimer's disease (AD), especially in men. Brain iron increases with age, is higher in men, and is abnormally elevated in several neurodegenerative diseases, including AD and Parkinson's disease, where it has been reported to contribute to younger age at onset in men. The effects of the common genetic variants (HFE H63D and/or TfC2) on brain iron were studied across eight brain regions (caudate, putamen, globus pallidus, thalamus, hippocampus, white matter of frontal lobe, genu, and splenium of corpus callosum) in 66 healthy adults (35 men, 31 women) aged 55 to 76. The iron content of ferritin molecules (ferritin iron) in the brain was measured with MRI utilizing the Field Dependent Relaxation Rate Increase (FDRI) method. 47% of the sample carried neither genetic variant (IRON-) and 53% carried one and/or the other (IRON+). IRON+ men had significantly higher FDRI compared to IRON- men (p=0.013). This genotype effect was not observed in women who, as expected, had lower FDRI than men. This is the first published evidence that these highly prevalent genetic variants in iron metabolism genes can influence brain iron levels in men. Clinical phenomena such as differential gender-associated risks of developing neurodegenerative diseases and age at onset may be associated with interactions between iron genes and brain iron accumulation. Clarifying mechanisms of brain iron accumulation may help identify novel interventions for age-related neurodegenerative diseases.

Ten-year experience with nephrogenic systemic fibrosis: case-control analysis of risk factors.

OBJECTIVES: To analyze all cases of nephrogenic systemic fibrosis (NSF) at our institution and to compare them with controls. METHODS: After the institutional review board approval, 13 biopsy-proven NSF cases were identified. Ten cases had complete records and were compared in a case-control format with 10 age- and sex-matched, dialysis-dependent controls. Analyzed risk factors included single and cumulative gadolinium dose, medication and transplant history, and serum electrolytes at the time of gadolinium exposure. RESULTS: There were 1.9% of dialysis-dependent, gadolinium-exposed patients who developed NSF. There was no difference in gadolinium dose, transplant history, or serum electrolytes. Seven of 10 cases and 3 of 10 controls were treated with erythropoietin (P = 0.13). At the time of NSF diagnosis, 7 of 10 cases were on immunosuppressive therapy. Two of 7 cases developed NSF only after immunosuppressive therapy was initiated. Two of 10 controls were on immunosuppressive therapy (P = 0.06). CONCLUSIONS: All cases of NSF occurred in dialysis-dependent, gadolinium-exposed patients. Associations between immunosuppressive and erythropoietin therapies and NSF need further investigation.

Supraaortic arteries: contrast material dose reduction at 3.0-T high-spatial-resolution MR angiography--feasibility study.

PURPOSE: To evaluate and compare the diagnostic image quality resulting from three contrast agent dose regimens for 3.0-T high-spatial-resolution three-dimensional magnetic resonance (MR) angiography of the supraaortic arteries. MATERIALS AND METHODS: Institutional review board approval was obtained; informed consent was waived for this HIPAA-compliant study. One hundred twenty consecutive patients who underwent 3.0-T three-dimensional high-spatial-resolution contrast material-enhanced MR angiography of the supraaortic arteries with an identical acquisition protocol were assigned to either the high-dose (0.154 mmol per kilogram of body weight), intermediate-dose (0.097 mmol/kg), or low-dose (0.047 mmol/kg) group. Two readers evaluated resulting images for arterial definition, venous contamination, and arterial stenosis. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated at six consistent sites. Statistical analysis was performed with the Kruskal-Wallis, Wilcoxon signed rank, and analysis of variance tests and the kappa coefficient. RESULTS: Readers 1 and 2 scored vascular definition as excellent or sufficient for diagnosis in 1311 of 1360 segments and in 1313 of 1360 segments in the high-dose group (kappa = 0.73), in 1321 of 1354 and in 1319 of 1354 segments in the intermediate-dose group (kappa = 0.77), and in 1322 of 1350 and in 1320 of 1350 segments in the low-dose group (kappa= 0.66), respectively. Arterial occlusive disease was detected by reader 1 in 52, 27, and 98 segments in the high-, intermediate-, and low-dose groups, respectively. Arterial occlusive disease was detected by reader 2 in 48, 25, and 100 segments in high-, intermediate-, and low-dose groups, respectively. No significant difference existed among the three groups regarding arterial definition scores (reader 1, P = .21; reader 2, P = .25) and venous contamination scores (reader 1, P = .38; reader 2, P = .35). SNRs and CNRs were lower in the low-dose group (P < .01). CONCLUSION: At 3.0 T, high-spatial-resolution MR angiography of the supraaortic arteries can be performed with contrast agent doses as low as 0.047 mmol/kg, without compromising image quality, acquisition speed, or spatial resolution. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/249/3/980/DC1http://radiology.rsnajnls.org/cgi/content/full/249/3/980/DC2.

Cystic adventitial disease of the popliteal artery: features on 3T cardiovascular magnetic resonance.

Cystic adventitial disease (CAD) of the popliteal artery is a rare vascular disease of unknown etiology in which a mucin-containing cyst develops in the adventitial layer of the artery. We report the case of a 26-year-old male with CAD of the right popliteal artery diagnosed non-invasively with 3 Tesla cardiovascular magnetic resonance and confirmed on post-operative histopathology.

Hypervascular thyroid nodules on time-resolved MR angiography at 3 T: radiologic-pathologic correlation.

OBJECTIVE: Detection of a thyroid nodule, either incidental or as a result of related symptomatology, is an extremely common event, often inducing considerable uncertainty regarding the requirement for and best means of further investigation. Whereas tissue sampling represents the sole means of true characterization of these lesions, a number of imaging characteristics have been suggested as potential indicators of the presence of malignancy. The potential value of time-resolved MR angiography, whereby a minimal dose of i.v. contrast agent is dynamically depicted during the first pass of the bolus through the various compartments of circulation, has recently been realized, particularly so with regard to supraaortic angiography. However, it is not uncommon during such temporal imaging to identify focal hyperenhancing thyroid nodules, the significance of which has not previously been described in the literature. We describe the frequency of occurrence and potential significance of this finding, using pathologic correlation where available. CONCLUSION: The prevalence of malignancy in incidentally detected focal hyperenhancing thyroid parenchymal nodules during time-resolved MR angiography is significant, representing 8.3% (1/12) of patients for whom cytologic correlation was available. Further investigation is certainly warranted when encountering such a lesion in clinical practice, particularly because it appears as though time-resolved MR angiography is of no value in the pathologic discrimination of such incidentally identified lesions.

MR angiography of lower extremities at 3 T: presurgical planning of fibular free flap transfer for facial reconstruction.

OBJECTIVE: The purpose of our study was to evaluate the use of preoperative MR angiography of the lower extremities at 3 T in candidates for fibular free flap harvesting, identifying atherosclerotic occlusive disease and congenital anomalies in this population. Our intention was to document the influence of the imaging findings on the surgical approach used. MATERIALS AND METHODS: Twenty-nine consecutive adult patients with facial abnormalities necessitating mandibular resection with subsequent osteocutaneous mandibular reconstruction who underwent preoperative MR angiography at 3 T were retrospectively reviewed. Images were evaluated by two observers with regard to image quality and visualization of arterial segments; severity of stenosis; and presence of noise, artifact, or venous contamination. The popliteal artery branching pattern present was also classified. The facial and reconstructive surgeon involved indicated whether the MR angiographic appearances influenced the decision regarding the side or location from which the flap was harvested or the flap design. RESULTS: Arterial segments were visualized with good or excellent image quality in 722 of 725 segments for observer 1 and 721 segments for observer 2. The kappa coefficient indicated good interobserver agreement (kappa = 0.78) with regard to quality of arterial segment depiction and scoring of stenoocclusive disease (kappa = 0.64). No segments had venous contamination, noise, or artifact of a degree sufficient to compromise diagnostic interpretation. Imaging influenced the surgical approach in 16 (55.2%) of 29 patients. CONCLUSION: Trifurcation vessel imaging should be a prerequisite to fibular free flap harvesting. High-spatial-resolution MR angiography at 3 T represents a desirable alternative to other invasive or cross-sectional imaging techniques in this regard.

Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications.

BACKGROUND: Postmortem and in vivo imaging data support the hypothesis that premature myelin breakdown and subsequent homeostatic remyelination attempts with increased oligodendrocyte and iron levels may contribute to Huntington's Disease (HD) pathogenesis and the symmetrical progress of neuronal loss from earlier-myelinating striatum to later-myelinating regions. A unique combination of in vivo tissue integrity and iron level assessments was used to examine the hypothesis. METHODS: A method that uses two Magnetic resonance imaging (MRI) instruments operating at different field-strengths was used to quantify the iron content of ferritin molecules (ferritin iron) as well as tissue integrity in eight regions in 11 HD and a matched group of 27 healthy control subjects. Three white matter regions were selected based on their myelination pattern (early to later-myelinating) and fiber composition. These were frontal lobe white matter (Fwm) and splenium and genu of the corpus callosum (Swm and Gwm). In addition, gray matter structures were also chosen based on their myelination pattern and fiber composition. Three striatum structures were assessed [caudate, putamen, and globus pallidus (C, P, and G)] as well as two comparison gray matter regions that myelinate later in development and are relatively spared in HD [Hippocampus (Hipp) and Thalamus (Th)]. RESULTS: Compared to healthy controls, HD ferritin iron levels were significantly increased in striatum C, P, and G, decreased in Fwm and Gwm, and were unchanged in Hipp, Th, and Swm. Loss of tissue integrity was observed in C, P, Fwm, and especially Swm but not Hipp, Th, G, or Gwm. This pattern of findings was largely preserved when a small subset of HD subjects early in the disease process was examined. CONCLUSIONS: The data suggest early in the HD process, myelin breakdown and changes in ferritin iron distribution underlie the pattern of regional toxicity observed in HD. Prospective studies are needed to verify myelin breakdown and increased iron levels are causal factors in HD pathogenesis. Tracking the effects of novel interventions that reduce myelin breakdown and iron accumulation in preclinical stages of HD could hasten the development of preventive treatments.