Complement and coagulation: causative considerations in contrast catastrophies.

Earlier studies suggest that adverse reactions to injected radiographic contrast media are idiosyncratic. In an attempt to gain a better understanding of pathophysiologic events underlying these reactions, rabbit models injected with lethal dose ranges of a cholangiographic contrast material were studied. These animals showed activation of both the complement and coagulation systems. Externally applied heat potentiated complement consumption and increased mortality. Depleting complement components C3-C9 by cobra venom factor did not prevent activation of coagulation or diminish mortality. However, depleting fibrinogen diminished complement activation and markedly diminished mortality. Heparin, administered at several hourly intervals after contrast challenge, also diminished mortality. These studies suggest that the adverse effects of contrast media in this model system are mediated chiefly by the coagulation system, and that complement, if it participates deleteriously, must involve components up to, but not including, C3. A logical role for the inhibitor of C1 esterase in adverse contrast reactions is considered.     

Heart rate reserve as a predictor of cardiovascular and all-cause mortality in men

This study examined the relationship of heart rate reserve (HRR: maximal heart rate - resting heart rate) and cardiovascular disease mortality (CVD) or all-cause mortality among healthy men. METHODS: Subjects were 27,459 healthy men, age 20-59 yr, who completed a maximal treadmill exercise test and answered a health questionnaire at the baseline examination. We followed study participants from the baseline visit to the date of death or December 31, 1996, for survivors. RESULTS: Over an average follow-up of 13.0 +/- 6.2 yr, there were 724 deaths, 205 (28.3%) from CVD. For analyses, the men were stratified into two age groups: younger (20-39 yr) and older (40-59 yr). Cox regression analysis was used to adjust for age, resting heart rate, cardiorespiratory fitness (CRF), resting systolic blood pressure (SBP), SBP difference, cholesterol, triglycerides, body mass index (BMI), smoking, and alcohol consumption. Among younger men, HRR was the only factor associated with CVD mortality (instantaneous relative risk (RR) and 95% confidence interval for HRR = 0.6, 0.5-0.9 for CVD mortality by 10 beats.min(-1) increment), whereas only CRF and BMI were associated with all-cause mortality. Among older men, HRR was inversely associated with CVD and all-cause mortality, as were several other known risk factors, including CRF (RR(per 2 METs), and 95% CI for HRR = 0.7, 0.5-0.9 for CVD mortality and 0.8, 0.7-0.9 for all-cause mortality). CONCLUSIONS HRR, independent from CRF, was inversely associated with CVD mortality among men in this study. HRR may be an important exercise test parameter to predict CVD mortality in younger men, whereas CRF and other established risk factors are better predictors of CVD and all-cause mortality in older men.     

Effect of site and rate of contrast material injection on pulmonary vascular distention

RATIONALE AND OBJECTIVES: The authors performed this study to determine if there were differences in vascular caliber measured on angiograms obtained with the injection protocol used for spiral computed tomography (CT) versus that used for pulmonary angiography. MATERIALS AND METHODS: The authors studied seven juvenile anesthetized pigs by using a prospective repeated measures experimental design. All pigs received injections of nonionic contrast material via catheters in the brachial vein, superior vena cava, main pulmonary artery, and left pulmonary artery. Weight-adjusted injection rates and volumes ranged from 0.05 mL/kg/sec (3.5 mL/sec, spiral CT protocol) to 0.56 mL/kg/sec (40 mL/sec, pulmonary angiography protocol). Heart rate and pulmonary artery and systemic artery pressures were recorded. During each injection, identically positioned pulmonary angiograms were obtained at full inspiration. Vessel diameters were measured at identical locations after each injection by two observers. The relationship between vessel diameter and hemodynamic parameters and injection site and rate was assessed with analysis of variance. RESULTS: At suspended full inspiration, no statistically significant difference (P > .05) in vessel diameter or hemodynamic parameters was found between the different injection sites or rates. There was no difference in vascular caliber between systole and diastole. CONCLUSION: The improved detection of subsegmental pulmonary emboli at pulmonary angiography compared with contrast material-enhanced spiral CT is not due to differences in vascular distention.     

Heart rate variability as a predictor of negative mood symptoms induced by exercise withdrawal

INTRODUCTION/PURPOSE: Negative mood symptoms occur frequently in sedentary populations, but individual vulnerability factors for developing these complaints have not been systematically evaluated. This investigation examined whether the autonomic nervous system (ANS) serves a role in the development of negative mood after controlled exercise withdrawal. METHODS: Forty participants (mean age of 31.3 +/- 7.5 yr, 55% women) who exercised regularly (>or= 30 min of continuous aerobic exercise at least three times a week during the past 6 months) were randomized either to withdrawal from regular aerobic exercise (N=20) or to continue regular aerobic exercise (N=20) for 2 wk. Measurements were taken before exercise withdrawal and at 2-wk follow-up. Various dimensions of negative mood were measured with the multidimensional fatigue inventory, profile of mood states, and Beck depression inventory-II. ANS activity was assessed by heart rate variability (HRV) analyses, examining low-frequency (0.04-0.15 Hz: lf) and high-frequency (hf) domains (0.15-0.40 Hz). The lf/hf ratio was used as index of sympathovagal balance. Protocol adherence was documented by ambulatory activity monitoring. RESULTS: Exercise withdrawal resulted in significantly higher negative mood scores at follow-up compared with control (P<0.05). Baseline lf/hf ratios correlated with the increases in symptoms (r>0.4; P<0.05) in the exercise-withdrawal group independently of gender, age, weight, baseline fitness level, and baseline symptom status. The exercise-withdrawal and control groups displayed no significant change in hf HRV, lf HRV, or lf/hf HRV during the 2 wk. CONCLUSION: Reduced parasympathetic ANS activity as measured by HRV is predictive of the development of negative mood after deprivation of usual exercise activities. No significant changes in HRV were observed during the 2-wk exercise deprivation period. These findings are relevant to the understanding of mood changes in response to short-term exercise withdrawal, such as sports injuries and recovery from medical procedures.     

Advertising of contrast material: a developing problem

Problems exist when indications for the use of new contrast agents and new indications for the use of conventional contrast agents are considered in relation to advertisements. Ultimately, the consumer pays the cost of expensive FDA testing, often to prove what is already obvious. Other medically indicated uses of a contrast agent may remain unapproved because there is no financial incentive to seek approval, and needed modifications in already approved advertisements may not be sought for the same reason. A cooperative effort among manufacturers, radiologists, and the FDA is needed to improve the process.     

Safety of contrast-enhanced MR angiography employing gadobutrol 1.0 M as contrast material

Our objectives were to evaluate the safety of intravenous 1.0-M gadobutrol injections in patients with an indication for contrast-enhanced magnetic resonance angiography (CE MRA) of supra-aortal, pelvic, or peripheral arteries by examining and assessing adverse events, laboratory values, vital signs and ECG findings for clinical significance. In 435 patients, recruited in three multicenter trials for safety evaluations of the new contrast agent 1.0-M gadobutrol, CE MRA was performed with 1.0- to 1.5-T scanners using three-dimensional gradient-echo sequences and phased-array coils. The study population comprised 312 men and 123 women with a mean age of 60.9 years. Two hundred seven patients had an indication for imaging of body arteries and 228 had an indication for imaging of peripheral arteries. Blood laboratory values and urinalysis results of 124 patients as well as heart rate, blood pressure, and 12-lead-electrocardiogram readings of 93 patients obtained during a follow-up period of up to 72 h after the injection of contrast media were available for safety analysis. Contrast media application was performed as intravenous bolus injection of 1.0-M gadobutrol in fixed doses according to the patients' body weight (b.w.) and indication for CE MRA and was followed by a 20- to 40-ml saline flush. Mean dose actually applied was 0.1 0.27 mmol/kg b.w. Flow rate ranged between 0.2 and 2.0 ml/s. Safety evaluations found a good tolerability with only 4.6% of at least "possibly related" adverse reactions and no clinically relevant changes in blood and urine samples including no transmetallation effect on serum zinc values. Analysis of renal tolerance showed no influence on renal function irrespective of preexisting renal impairment. The ECG analysis (rhythm analysis, pace-setting disturbances, conduction disturbances, and time interval measurements, including uncorrected and corrected QT) showed no clinically relevant effect of the injection of 1.0-M gadobutrol on the cardiac conduction system. Intravenous injection of 1.0-M gadobutrol at a dose of up to 0.1 0.27 mmol/kg b.w. in the indication CE MRA is safe and causes no clinically relevant changes in safety parameters such as heart rate, blood pressure, blood and urine laboratory values, and cardiac conduction system.     

Percutaneous renal stone removal. Use of carbon dioxide as contrast material

The successful performance of a percutaneous nephrostomy requires contrast material in the renal collecting system. For an exact delineation of all renal calices in a patient allergic to iodine, carbon dioxide was injected into the renal pelvis. The stone was removed successfully.     

Multidetector CT of pancreas: effects of contrast material flow rate and individualized scan delay on enhancement of pancreas and tumor contrast

PURPOSE: To prospectively assess whether high contrast material flow rate (8 mL/sec) and individualized scan delay improve enhancement of normal pancreas with multidetector computed tomography (CT) and, as a result, tumor-to-pancreas contrast of pancreatic adenocarcinoma. MATERIALS AND METHODS: Informed consent was obtained in 40 patients (21 women, 19 men; mean age, 67.1 years); the institutional review board approved this protocol. Patients were referred for multidetector CT because they were suspected of having a pancreatic tumor and were randomized to receive 150 mL of nonionic contrast material (300 mg of iodine per milliliter) at a flow rate of 4 mL/sec (n = 21) or 8 mL/sec (n = 19). Patients underwent dynamic scanning at one level every 2 seconds for 66 seconds after intravenous administration of contrast material. Contrast enhancement of pancreas and tumors was measured with circular regions of interest (analysis of variance and Bonferroni-Holm corrected post hoc t tests). RESULTS: Peak contrast enhancement in pancreas was observed significantly earlier (mean +/- standard deviation, 28.7 seconds +/- 3.5 vs 48.2 seconds +/- 5.3; P < .05) and was significantly higher (129.0 HU +/- 25.7 vs 106.2 HU +/- 35.4, P < .05) with a flow rate of 8 mL/sec than with a flow rate of 4 mL/sec. Tumor-to-pancreas contrast greater than 40 HU lasted significantly longer with a flow rate of 8 mL/sec than with a flow rate of 4 mL/sec (26.4 seconds +/- 11.9 vs 8.6 seconds +/- 8.3, P < .05). With a flow rate of 8 mL/sec, an individualized scan delay of 19 seconds after aortic transit time revealed higher tumor-to-pancreas contrast than did a fixed scan delay, and tumor conspicuity was better. CONCLUSION: With 16-section CT, increased contrast material flow rate of 8 mL/sec and individualized scan delay were associated with improved pancreatic enhancement and tumor-to-pancreas contrast compared with flow rate of 4 mL/sec and fixed scan delay.     

Magnetite albumin microspheres: a new MR contrast material

A superparamagnetic MR contrast agent was synthesized by incorporating 150-250-A particles of magnetite (Fe3O4, Fe2O3) in 1-5 microns human serum albumin microspheres. Magnetite albumin microspheres (MAM) target almost exclusively to the reticuloendothelial system after IV administration, are stable in vitro and in vivo, and possess a long shelf life. The agent has a large magnetic susceptibility effect that selectively reduces T2 with little effect on T1. Biodistribution studies that use a dose of 20 mg MAM/kg show prompt clearance from the blood pool with marked decrease in T2 for rat liver (40%) and spleen (45%) with a small decrease in liver (5%) and spleen (10%) T1 values. Pulmonary T1 and T2 decrease transiently over the first 24 hr, while no significant changes were observed in other tissues. Imaging of a rabbit VX2 tumor model resulted in a 200% increase in the contrast ratio of VX2 tumor to normal liver on T2-weighted and mixed T1-/T2-weighted pulse sequences after administration of contrast agent. The extreme potency, excellent targeting, and apparent lack of toxicity of this agent suggest that MAM probably will have a clinical application in detecting focal hepatic and splenic lesions.     

Cutaneous reaction to contrast material

Two children are described who developed an apparent cutaneous contact reaction to contrast material in urine. Both children had undergone uneventful voiding cystourethrography with diatrizoate meglumine injection USP 18% followed by intravenous urography with diatrizoate meglumine injection USP 60%. Approximately 1 hour after urography cutaneous bullae and surrounding erythema of the buttocks (one case) or foreskin (one case) were noted. This reaction resembled a superficial chemical burn.     

16-MDCT aortography with a low-dose contrast material protocol

OBJECTIVE: The objective of our study was to evaluate whether a low-dose contrast material (CM) protocol with a saline flush might provide sufficient contrast enhancement in aortoiliac 16-MDCT angiography. SUBJECTS AND METHODS: Forty-five patients were divided into two groups on the basis of the CM (300 mg I/mL) administration protocol: group 1 (23 patients) received 100 mL of CM at 3.0 mL/sec; and group 2 (22 patients), 50 mL of CM at 3.0 mL/sec followed by a 20-mL saline flush at 3.0 mL/sec. All patients underwent 16-MDCT angiography of the entire aortoiliac region. Seven regions of interest (ROIs) were drawn from the ascending aorta (ROI 1) to the external iliac artery (ROI 7). Quantitative analysis was performed by calculating the mean aortoiliac attenuation and the mean difference between the maximum and minimum attenuation values. Vascular enhancement of the renal arteries was visually assessed using 2D and 3D postprocessing techniques. RESULTS: The mean aortoiliac attenuation in group 1 was 314.3 +/- 45.9 H and that in group 2 was 306.1 +/- 35.0 H. The difference was not statistically significant. Adequate mean aortoiliac attenuation was achieved in 95.7% (22/23) and 95.5% (21/22) of patients in groups 1 and 2, respectively. The difference was not statistically significant. The mean difference between the maximum and minimum attenuation values was significantly smaller in group 1 (41.3 +/- 16.8 H) than in group 2 (57.2 +/- 25.3 H). The renal arteries were assessable in all patients in both groups. CONCLUSION: This protocol of 50 mL of CM with a saline flush provides attenuation comparable to that obtained with the 100 mL of CM in aortoiliac 16-MDCT angiography.     

Utility of different MR modalities in mild cognitive impairment and its use as a predictor of conversion to probable dementia

RATIONALE AND OBJECTIVES: Mild cognitive impairment has been regarded as a pre-Alzheimer condition, but some patients do not develop dementia. The authors' objective was to determine whether findings from a combined use of H1 magnetic resonance spectroscopy (MRS), perfusion imaging (PI), and diffusion-weighted imaging (DWI) would predict conversion from amnesic mild cognitive impairment to dementia and to compare the diagnostic accuracy in discriminating patients with probable Alzheimer disease (AD), mixed dementia (MD), Lewy body dementia (LBD), pre-Alzheimer disease mild cognitive impairment (MCI), vascular MCI (VaMCI), and anxious or depression patients with cognitive impairment (DeMCI). MATERIALS AND METHODS: A longitudinal cohort of 119 consecutive and incident subjects (73 women, 46 men; age 70 +/- 9.5 years) who fulfilled the criteria of amnesic MCI was followed for a mean period of 29 months. At baseline, a neuropsychological examination and standard blood test were performed, and different areas were examined by proton MRS, PI, and DWI. Among the group of patients considered to have AD, we also included patients with MD because these patients have a neurodegenerative component. RESULTS: After the follow-up period, 54 patients were considered as converted to dementia (49 with AD; 5 with LBD), 28 patients as MCI, 22 patients as DeMCI, and 15 patients as VaMCI. We found that N-acetylaspartate (NAA)/creatine (Cr) ratios in posterior cingulated gyri (PCG) predict the conversion to probable AD with a sensitivity of 82% and specificity of 72%, and NAA/Cr ratios in the left occipital cortex (LOC) had a sensitivity of 78% and specificity of 69%. When we used spectroscopy in the PCG and LOC to differentiate the types of MCI and dementias, we found significance differences in NAA/Cr, NAA/myoinositol (mI), NAA/choline (Cho), mI/NAA, and Cho/Cr ratios. The apparent diffusion coefficient (ADC) values in the right hippocampus showed differences in patients with LBD and DeMCI (P = .003), LBD with MCI (P = 0.48), and LBD and VaMCI (P = .009). CONCLUSIONS: NAA/Cr ratios in PCG and LOC can predict the conversion from MCI to dementia with high sensitivity and specificity. MRS can differentiate AD from MCI, but cannot differentiate the types of MCI. DWI in the right hippocampus presents higher values of ADC in LBD and allows differentiating it from MCI.