An approach to evaluate myocardial perfusion defect assessment for projection-based DECT: A phantom study.

INTRODUCTION: Dual-energy CT (DECT) can improve the accuracy of myocardial perfusion CT with projection-based monochromatic (DECT-MCE) and quantification of myocardial iodine in material decomposition (DECT-MD) reconstructions. However, evaluation of multiple reconstructions is laborious and the optimal reconstruction to detect myocardial perfusion defects is unknown. METHODS: Left ventricular (LV) phantoms with artificial perfusion defects were scanned using DECT and single energy cardiac computed tomography angiography (SECT). Reconstructions of DECT-MCE at 40, 70, 100 and 140 keV, DECT-MD pairs of water, iodine, iron and fat, and SECT were evaluated using a 17-segment myocardial model. The diagnostic performance of each reconstruction was calculated on a per-segment basis and compared across DECT reconstructions. RESULTS: Over 34 phantoms with artificial perfusion defects were found in 64/578 (11%) of segments, the sensitivity of DECT-MCE at 40, 70, 100, and 140 keV was 100% (95% confidence interval (CI): 93-100), 100% (95% CI: 93-100), 71% (95% CI: 56-83), and 25% (95% CI: 14-40), respectively, with a significant decline between 70 keV and 100 keV (p < 0.001). The specificity of DECT-MCE was 100% at all energies (95% CI: 99-100). As a group, the DECT-MD iodine background reconstructions had significantly lower sensitivity than the remaining modes (2.1% [95% CI, 0.05-11.1], vs. 100% [95% CI, 92.6-100], p < 0.001). Specificity of all material pair modes remained 100%. CONCLUSIONS: Using LV phantom models, the approach with the best sensitivity and specificity to assess myocardial perfusion defects with DECT are reconstructions of DECT-MCE at 40 or 70 KeV and DECT-MD without iodine background.

Cyberbullying and Adolescents.

PURPOSE OF REVIEW: Cyberbullying is an aggressive behavior involving a type of electronic communication intending to harm a victim that can have profound effects on adolescents. This review examines the epidemiology, issues from cyberbullying, presentation to care of its victims and proposed interventions to this behavior. RECENT FINDINGS: There are a variety of physical and psychological effects on victims of cyberbullying that can include recurrent abdominal pain, headaches and difficulty with sleep. In addition, victims have higher rates of anxiety, depression, suicidal ideation and a lower level of well-being. Unfortunately, victims may remain silent, so screening for cyberbullying is encouraged in a variety of settings. Interventions can be designed at the level of the victim (and perpetrator), family, school and other support networks. Prevention of cyberbullying can be a focus for providers of healthcare. SUMMARY: Cyberbullying can have profound biopsychosocial effects on its victims. There are strategies currently in use and under development to identify and intervene on behalf of those affected by these behaviors.

Estimation of myocardial fibrosis in humans with dual energy CT.

BACKGROUND: The current clinical standard for in vivo imaging of myocardial fibrosis is contrast-enhanced cardiac magnetic resonance (CMR). We sought to validate a novel non-contrast dual energy computed tomography (DECT) method to estimate myocardial fibrosis in patients undergoing CMR with contrast. METHODS: All subjects underwent non-contrast, prospectively-triggered cardiac DECT on a single source scanner with interleaved acquisition between tube voltages of 80 and 140 kVp. Monochromatic images were reconstructed at 11 energies spanning 40-140 keV; a region of interest (ROI) was drawn in the mid-inferoseptal segment, recording mean attenuation value in the ROI, at each energy level. Comparison was made to data from single energy (70 keV) image data. Linear discriminant analysis (LDA) was performed to compare the predictive capability of single vs. multi-energy inferoseptal segment CT attenuation on myocardial fibrosis by both visually assessed LGE (absent/present fibrosis) and CMR T1 mapping-derived myocardial extracellular volume fraction (ECV). RESULTS: The multi-energy CT/LDA approach performed better than a single energy approach to discriminate among LGE-CMR classes of present/absence myocardial fibrosis severity, demonstrating correct classification rates of 89% and 71%, respectively. The multi-energy CT/LDA approach also performed better in correctly discriminating normal from elevated ECV, doing so in 89% of patients vs. correct distinction of normal/elevated ECV in only 70% using the single energy approach. CONCLUSIONS: Non-contrast cardiac DECT with multi-energy analysis better classifies myocardial fibrosis and extracellular volume compared to what is feasible with non-contrast single energy cardiac CT. These data support further evaluation of this approach to noninvasively assess myocardial fibrosis.

Acute pancreatitis secondary to the use of the anabolic steroid trenbolone acetate.

BACKGROUND: The use of performance-enhancing drugs has increased dramatically in the last decade with high prevalence reported among the young athlete population. Many of these drugs contain anabolic steroids and may carry potential significant side effects and health risks. We report a case of anabolic steroid-induced acute pancreatitis (AP) that recurred after the reuse of the same drug by the patient, confirming the causative relationship. CASE REPORT: A 24 year-old male presented with severe epigastric pain. His past medical history was significant for two hospitalizations during the last year with AP. During his hospital admissions, extensive workup was performed ruling out the common and uncommon causes of AP. Upon further pressing, the patient admitted to a history of past and current anabolic steroid use for athletic performance enhancement. He began this use four years ago and most recently started using trenbolone acetate (TA). The correlation between the timing of the anabolic steroids administration and the attacks of AP, along with ruling out other causes, confirmed TA as the cause of pancreatitis. DISCUSSION: The side effects associated with the use of these increasingly prevalent drugs are difficult to study in clinical trials due to the unethical nature of their consumption. In addition, these medications are difficult to study due to the varied usage cycles and patterns, unknown origin and source, as well as often high dose ingestion. Physicians and body builders need to be aware of the possible serious consequences of their use.

Correction: Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability.

Since the publication of the above article, the authors have noted that the name of the first Item in the NRAS scoring system in Figure 1 was omitted. It is Heart Rate (C1). The authors apologise for any inconvenience caused by this error. The html and online pdf versions have now been rectified and carry the corrected Figure.

Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability.

OBJECTIVE: To test the non-inferiority of an alternative to the Apgar score. STUDY DESIGN: The Neonatal Resuscitation and Adaptation Score (NRAS) was recorded in parallel to the Apgar score by a resuscitation team at deliveries. Correlation between the systems was assessed, as well as the predictive ability of NRAS and Apgar scores for mortality or short-term morbidities. RESULTS: A total of 340 infants were in the study group. The two scores correlated strongly (r = 0.87 and 0.83 at 1 and 5 min, respectively). Those needing ventilation at 48 h of life had a 5-min NRAS < 7 in 23/26 vs Apgar < 7 (23/36, p = 0.001). A low (0-3) 1-min NRAS score was more predictive of death, 53% vs 17%, p = 0.0065. CONCLUSIONS: NRAS correlates with Apgar status assessment, and identifies newborns who die or may require further care better than the Apgar score.

Non-contrast estimation of diffuse myocardial fibrosis with dual energy CT: A phantom study.

BACKGROUND: Estimation of diffuse myocardial fibrosis, substrate for adverse events such as heart failure and arrhythmias in patients with various cardiac disorders, is presently done by histopathology or cardiac magnetic resonance. We sought to develop a non-contrast method to estimate the amount of diffuse myocardial fibrosis leveraging dual energy computed tomography (DECT) in phantoms and a suitable small animal model. METHODS AND RESULTS: Phantoms consisted of homogenized bovine myocardium with varying amounts of Type 1 collagen. Fifteen mice underwent sham surgery, no procedure, or transverse aortic constriction (TAC) for 5 or 8 weeks to produce moderate or severe fibrosis, respectively. Phantoms and ex vivo mouse hearts were imaged on a single source, DECT scanner equipped with kVp switching. Monochromatic images were reconstructed at 40-140 keV. Linear discriminant analysis (LDA) was performed on mean myocardial CT numbers derived from single energy (70 keV) images as well as images reconstructed across multiple energies. Classification of myocardial fibrosis severity as low, moderate or severe was more often correct using the multi-energy CT/LDA approach vs. single energy CT/LDA in both phantoms (80.0% vs. 70.0%) and mice (93.3% vs. 33.3%). CONCLUSIONS: DECT myocardial imaging with multi-energy analysis better classifies myocardial fibrosis severity compared to a single energy-based approach. Non-contrast DECT can accurately and non-invasively estimate the extent of diffuse myocardial fibrosis in phantom and animal models. These data support further evaluation of this approach for in vivo myocardial fibrosis estimation.

Multiorgan, Multimodality Imaging in Cardiometabolic Disease.

Cardiometabolic disease, spanning conditions such as obesity to type 2 diabetes mellitus with excess cardiovascular risk, represents a major public health burden. Advances in preclinical translational science point to potential targets across multiple organ systems for early intervention to improve cardiometabolic health. Validation in clinical trials and translation to care would benefit from in vivo diagnostic techniques that facilitate therapeutic advancements. This review provides a state-of-the-art, multimodality perspective spanning the multiple organ systems that contribute to cardiometabolic disease.

Evaluation of antitumor activity and cardiac toxicity of a bone-targeted ph-sensitive liposomal formulation in a bone metastasis tumor model in mice.

Chemotherapy for bone tumors is a major challenge because of the inability of therapeutics to penetrate dense bone mineral. We hypothesize that a nanostructured formulation with high affinity for bone could deliver drug to the tumor while minimizing off-target toxicity. Here, we evaluated the efficacy and toxicity of a novel bone-targeted, pH-sensitive liposomal formulation containing doxorubicin in an animal model of bone metastasis. Biodistribution studies with the liposome showed good uptake in tumor, but low accumulation of doxorubicin in the heart. Mice treated with the bone-targeted liposome formulation showed a 70% reduction in tumor volume, compared to 35% reduction for free doxorubicin at the same dose. Both cardiac toxicity and overall mortality were significantly lower for animals treated with the bone-targeted liposomes compared to free drug. Bone-targeted, pH-sensitive, doxorubicin containing liposomes represent a promising approach to selectively delivering doxorubicin to bone tumors while minimizing cardiac toxicity.

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle.

Skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, which is critically important in health and disease, can be measured in vivo and noninvasively in humans via phosphorus-31 magnetic resonance spectroscopy (31PMRS). However, the approach has not been widely adopted in translational and clinical research, with variations in methodology and limited guidance from the literature. Increased optimization, standardization, and dissemination of methods for in vivo 31PMRS would facilitate the development of targeted therapies to improve OXPHOS capacity and could ultimately favorably impact cardiovascular health. 31PMRS produces a noninvasive, in vivo measure of OXPHOS capacity in human skeletal muscle, as opposed to alternative measures obtained from explanted and potentially altered mitochondria via muscle biopsy. It relies upon only modest additional instrumentation beyond what is already in place on magnetic resonance scanners available for clinical and translational research at most institutions. In this work, we outline a method to measure in vivo skeletal muscle OXPHOS. The technique is demonstrated using a 1.5 Tesla whole-body MR scanner equipped with the suitable hardware and software for 31PMRS, and we explain a simple and robust protocol for in-magnet resistive exercise to rapidly fatigue the quadriceps muscle. Reproducibility and feasibility are demonstrated in volunteers as well as subjects over a wide range of functional capacities.

Computation of Calcium Score With Dual-Energy Computed Tomography: A Phantom Study.

Dual-energy computed tomography (DECT) improves material and tissue characterization compared with single-energy CT; we sought to validate coronary calcium quantification in advancing cardiovascular DECT. In an anthropomorphic phantom, agreement between measurements was excellent, and Bland-Altman analysis demonstrated minimal bias. Compared with the known calcium mass for each phantom, calcium mass by DECT was highly accurate. Noncontrast DECT yields accurate calcium measures and warrants consideration in cardiac protocols for additional tissue characterizations.

Noninvasive Assessment of Losartan-Induced Increase in Functional Microvasculature and Drug Delivery in Pancreatic Ductal Adenocarcinoma.

PURPOSE: Losartan, an angiotensin II receptor blocker, can reduce desmoplasia and enhance drug delivery and efficacy through improving interstitial transport and vascular perfusion in pancreatic ductal adenocarcinoma (PDAC) models in mice. The purpose of this study was to determine whether magnetic resonance imaging (MRI) of magnetic iron oxide nanoparticles (MNPs) and micro-positron emission tomography (PET) measurements could respectively detect improvements in tumor vascular parameters and drug uptake in orthotopic PDAC in mice treated with losartan. METHOD AND MATERIALS: All experiments were approved by the local Institutional Animal Care and Use Committee. FVB mice with orthotopic PDAC were treated daily with an i.p. injection of losartan (70 mg/kg) or saline (control vehicle) for 5 days. In order to calculate the fractional blood volume, vessel size index, and vessel density index, MRI was performed at 4.7 T following the injection of 3 mg/kg iron ferumoxytol (i.v.). Dynamic PET images were also acquired for 60 minutes using an 18F-5FU tracer dose of 200 µCi and analyzed for time activity curves normalized to muscle. Statistical analyses compared both cohorts using an unpaired two-tailed t test. RESULTS: In comparison to the control treatment, the losartan administration significantly increased the fractional blood volume (mean±SEM) [12.1±1.7 (n=19) vs 6.7±1.1 (n=20); P<.02] and vessel size index (128.2±35.6 vs 57.5±18; P<.05). Losartan also induced a significant increase in the intratumoral uptake of 18F-5FU by 53% (P<.0001). CONCLUSION: MRI using FDA-approved MNPs provides a noninvasive, translatable means of assaying microvascular parameters induced by losartan in pancreatic cancer. PET measurements demonstrated that losartan significantly increased the uptake of 18F-5FU.

Peroneal tendon abnormalities in subjects with an enlarged peroneal tubercle.

OBJECTIVE: To examine the association between inframalleolar peroneal tendon abnormalities and an enlarged peroneal tubercle. MATERIALS AND METHODS: Two independent readers evaluated consecutive ankle MR imaging studies to classify inframalleolar peroneal tendon findings as normal, tenosynovitis, partial tear or complete tear. The size and morphology of the peroneal tubercle was also recorded. We performed statistical analyses for inter-observer agreement and to assess differences in peroneal tubercle size between groups with and without peroneal tendon abnormalities. RESULTS: The study group comprised 121 subjects (mean age, 45.5 years) of whom 28% (34 out of 121) had lateral ankle symptoms. The peroneal tubercle was absent in 56% of subjects (68 out of 121). In subjects with a peroneal tubercle (>0 mm), the mean size was 3.5 mm (37% triangular and 7% plateau-shaped). Male subjects had significantly larger mean peroneal tubercle size than female subjects (2.1 ± 2.5 vs 1.2 ± 1.9 mm, P = 0.04). Overall, 26% (32 out of 121) of subjects had some peroneal tendon abnormality: 17% (20 out of 121) had tenosynovitis and 17 % (20 out of 121) had partial thickness tears. The peroneal tubercle size was significantly larger in subjects with peroneal tendon partial tears (P = 0.036), tenosynovitis (P < 0.001), and when both abnormalities were present (P = 0.007). ROC statistic showed 73% sensitivity and 74% specificity for detection of partial tears for peroneal tubercle size ≥4.3 mm. CONCLUSION: Our study shows a significantly larger peroneal tubercle in subjects with inframalleolar peroneal tendon abnormalities. A cut-off of 4.3 mm showed good sensitivity and specificity for the presence of partial tears of the peroneal tendon.

Ectopic and serum lipid levels are positively associated with bone marrow fat in obesity.

PURPOSE: To investigate the associations between ectopic and serum lipid levels and bone marrow fat, as a marker of stem cell differentiation, in young obese men and women, with the hypothesis that ectopic and serum lipid levels would be positively associated with bone marrow fat. MATERIALS AND METHODS: The study was institutional review board approved and complied with HIPAA guidelines. Written informed consent was obtained. The study group comprised 106 healthy young men and women (mean age, 33.7 years ± 6.8 [standard deviation]; range, 19-45 years; mean body mass index (BMI), 33.1 kg/m(2) ± 7.1; range, 18.1-48.8 kg/m(2)) who underwent hydrogen 1((1)H) magnetic resonance (MR) spectroscopy by using a point-resolved spatially localized spectroscopy sequence at 3.0 T of L4 for bone marrow fat content, of soleus muscle for intramyocellular lipids (IMCL), and liver for intrahepatic lipids (IHL), serum cholesterol level, serum triglyceride level, and measures of insulin resistance (IR). Exercise status was assessed with the Paffenbarger activity questionnaire. RESULTS: There was a positive correlation between bone marrow fat and IHL (r = 0.21, P = .048), IMCL (r = 0.27, P = .02), and serum triglyceride level (r = 0.33, P = .001), independent of BMI, age, IR, and exercise status (P < .05). High-density lipoprotein cholesterol levels were inversely associated with bone marrow fat content, independent of BMI, age, IR, and exercise status (r = -0.21, P = .019). CONCLUSION: Results of this study suggest that ectopic and serum lipid levels are positively associated with bone marrow fat in obese men and women.

Similar trends in serum VEGF-D levels and kidney angiomyolipoma responses with longer duration sirolimus treatment in adults with tuberous sclerosis.

CONTEXT: We have previously shown that serum VEGF-D is elevated at baseline, correlates with kidney angiomyolipoma size at baseline and 12 months, and decreases with sirolimus treatment in adults with tuberous sclerosis complex (TSC). To further investigate the utility of serum VEGF-D for longer term monitoring of TSC kidney disease, we present VEGF-D level results with 24 month follow-up. OBJECTIVE: To compare 24 month VEGF-D levels in two subgroups of sirolimus treated patients (OFF SIROLIMUS AFTER 12 MONTHS or ON SIROLIMUS AFTER 12 MONTHS). DESIGN AND INTERVENTION(S): Serum VEGF-D was measured in samples collected from subjects enrolled in a phase 2 multicenter trial evaluating sirolimus for the treatment of kidney angiomyolipomas associated with TSC or TSC/LAM. All participants were treated with sirolimus from 0-12 months. During months 12-24, sirolimus was discontinued in one subgroup. The other subgroup was treated with additional sirolimus. SETTING: Adult TSC participants were recruited from six clinical sites in the United States (comprehensive TSC clinics, 5; urology clinic, 1). PATIENTS: There were 28 TSC patients who completed all 24 months of the study and serum samples were available at 24 months from 18/28 patients. MAIN OUTCOME MEASURE(S): We compared the percent change in VEGF-D levels (baseline to 24 months) in patients from the two treatment subgroups. RESULTS: At 24 months, VEGF-D levels decreased by 67% compared with baseline (to 787 ± 426 pg/ml) in the ON SIROLIMUS AFTER 12 MONTHS group versus a 13% decrease (to 2971 ± 4014 pg/ml) in the OFF SIROLIMUS AFTER 12 MONTHS group (p=0.013, Mann-Whitney test). A similar trend was observed in kidney angiomyolipoma size but not in pulmonary function tests. Conclusions Serum VEGF-D may be useful for monitoring response to treatment with sirolimus and kidney angiomyolipoma size in patients with TSC, but confirmation is needed. TRIAL REGISTRATION: Clinical trials.gov NCT00126672.