Radiation safety issues with high activities of liquid I-125: techniques and experience.

The handling of a liquid radioactive source is a procedure that is uncommon for the average clinical medical physicist. A newly approved treatment device utilizes high activities of liquid I-125 solution as the source of radiation. The radiation safety issues and our experience utilizing high activity liquid I-125 sources are presented. To date we have treated 22 patients with infused activities ranging up to 26.8 GBq (724 mCi). The careful manipulation of such solutions is important to maintain a safe environment for the patients and the involved medical staff.

Insulin resistance and fat patterning with aging: relationship to metabolic risk factors for cardiovascular disease.

Both insulin resistance and abdominal fat patterning are related to aging, and have been related to cardiovascular disease (CVD) risk factors such as dyslipidemia and hypertension. However, previous studies have not used direct methods to quantify the independent strength of the association of each of these two putative primary factors with metabolic outcomes. We quantified overall obesity by the body mass index (BMI) and used a previously validated magnetic resonance imaging (MRI) method to quantify abdominal fat in 63 healthy nondiabetic individuals aged 22 to 83 years. We also measured the glucose and insulin response to an oral glucose tolerance test and the insulin sensitivity ([SI] by modified minimal model analysis). Body fat patterning was evaluated by the waist to hip ratio (WHR) and by MRI, which allowed direct measurement of subcutaneous (SCF) and intraabdominal (IAF) fat depots at the umbilicus in these subjects. These independent parameters were related to risk factors for CVD (blood pressure, lipids, and lipoproteins) and to plasma concentrations of free fatty acids (FFAs). Measures of overall obesity (BMI), total fat [TF], and/or SCF measured at the abdomen by MRI), glucose/insulin metabolism and SI, and central fat patterning (WHR or IAF measured by MRI) were correlated with mean arterial pressure (MAP), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels in univariate analysis and after controlling for age and gender. An index of central fat patterning (WHR) added to the informativeness of the insulin area under the curve (IAUC) in explaining 24% of the variability in plasma TG concentration, but measures of overall obesity were not independently related. Both the BMI and TF contributed to the IAUC in explaining 32% to 34% of the variability in MAP, but central fat patterning was not independently related. No index of overall obesity, fat patterning, glucose/insulin metabolism, and/or SI, was independently related to the plasma concentration of HDL-C after controlling for any one of the other two. Direct measurement of glucose/insulin metabolism and SI, as well as fat patterning, provides information on their relative associations with CVD risk factors. The measures of glucose/insulin metabolism and SI were more consistently related to dyslipidemia and hypertension than were the overall obesity and fat patterning in this healthy population.

Sex-specific associations of magnetic resonance imaging-derived intra-abdominal and subcutaneous fat areas with conventional anthropometric indices. The Atherosclerosis Risk in Communities Study.

Accurate measurement of central fat patterning is difficult to obtain by conventional anthropometry. Direct measurement of intra-abdominal fat area by magnetic resonance imaging, while accurate, is impractical for large-scale observational studies. This report examines the sex-specific associations of conventional anthropometric indices with intra-abdominal fat and subcutaneous fat areas measured by magnetic resonance imaging. A total of 157 volunteers (97 men and 60 women) aged 48-68 years of predominately white ethnicity had intra-abdominal fat and subcutaneous fat areas measured as part of the Atherosclerosis Risk in Communities (ARIC) Study. Weight, body mass index, waist circumference, waist : hip ratio, and subscapular skinfold thickness were measured or calculated by a standardized protocol. On average, women had a lower intra-abdominal fat area than men (109.5 cm2 vs. 152.9 cm2) but a higher mean subcutaneous fat area (287.8 cm2 vs. 214.6 cm2). After adjustment for age, intra-abdominal fat area was quadratically associated with body mass index, waist circumference, weight, and subscapular skinfold thickness in men; in women, these associations were best modeled by a positive linear equation. Waist : hip ratio was linearly related to intra-abdominal fat area in both sexes. In general, anthropometric measures predicted lower percentages of the total variance in intra-abdominal fat area for men than for women. For subcutaneous fat area, all anthropometric indices were linearly associated and predicted more of the variance in subcutaneous fat area than in intra-abdominal fat area. These results indicate that among men, greater intra-abdominal fat deposition rates occur at relatively low body weights and fat is more uniformly deposited at higher weights. Women appear to deposit intra-abdominal fat at a constant rate as they gain weight, even after menopause. The authors conclude that when waist circumference or body mass index is used as a surrogate for intra-abdominal fat area in men, a quadratic term should be included in the analysis as a predictor variable. Subcutaneous fat area can be estimated well by linear measures commonly employed in epidemiologic studies.

Evaluation of magnetic resonance imaging for quantification of intraabdominal fat in human beings by spin-echo and inversion-recovery protocols.

We evaluated two magnetic resonance imaging (MRI) methods, spin echo and inversion recovery (IR), for quantification of intraabdominal fat in a subgroup of participants from the Atherosclerosis Risk in Communities (ARIC) Study. Both methods were used previously to quantify visceral fat, and the IR but not the spin echo method has been validated by comparison with computed tomography in human beings. In the present study, the reliability of both methods was excellent: reliability coefficients comparing two readers on the same scan were 0.9574 for IR (n = 158) and 0.9254 for spin echo (n = 47) when random effects models with log-transformed data were used. A comparison of visceral fat areas in 47 subjects with both IR and spin echo indicated that IR gave a slightly higher mean area than did spin echo: 134.9 compared with 129.8 cm2. However, a mixed-model analysis of variance (ANOVA) of the log-transformed data showed no statistical difference between either method or readers in the comparison of IR and spin echo. These data suggest that the IR and spin echo protocols evaluated in this communication are comparable with one another and reliable for estimation of intraabdominal fat.

Contribution of visceral fat mass to the insulin resistance of aging.

Recent studies have shown that central obesity (increased waist to hip ratio [WHR]) is related to insulin resistance and aging. Furthermore, in central-obesity states, the intraabdominal fat (IAF) depot has been postulated to contribute most to the development of insulin resistance. Therefore, the observed insulin resistance of aging may be related more to changes in body composition than to aging per se. The purpose of this study was to explore the association of IAF with age and insulin sensitivity (SI) after controlling for obesity. We examined 60 healthy nondiabetic subjects (normal 75-g oral glucose tolerance test, aged 23 to 83, 15 men and 45 women). We chose subjects so that those < or = 125% and greater than 125% of ideal body weight were equally represented in each age decade. We quantified total and subcutaneous abdominal fat and IAF at the umbilicus using a validated magnetic resonance imaging (MRI) scanning technique and determined SI using a modified minimal model. IAF correlated significantly with age (r = .49, P = .0001) in the group as a whole, as well as in men (r = .58, P = .022) and women (r = .48, P = .0008) separately. In all subjects, SI was significantly related to IAF (r = -.50, P < .0001) but was not related to age (r = .00, P = .98). In multivariate analysis for various combinations of age, sex, and measures of fat distribution, WHR accounted for 28% and IAF for 51% of the variance in SI, whereas age, sex, and interactions of age and sex accounted for only 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of intraabdominal fat as measured by magnetic resonance imaging to postprandial lipemia in middle-aged subjects.

Adipose distribution has been associated with coronary artery disease and its risk factors. We previously described an association between postprandial triglyceride response (pptg response) to a standard high-fat meal and extracranial carotid atherosclerosis. This study was designed to evaluate the association between intraabdominal fat and pptg response. Twenty-nine subjects were recalled for determination of intraabdominal fat by magnetic resonance imaging (MRI). Fat was quantified according to an inversion recovery protocol previously validated and the cross-sectional area of intraabdominal fat at the umbilicus was analyzed as an independent variable. We observed a strong independent correlation between intraabdominal fat and pptg response to a fatty meal (r = 0.521, P < 0.05). Baseline triglyceride was also independently correlated with postprandial triglycerides (r = 0.631, P < 0.05). In univariate analysis, intraabdominal fat was correlated with age, sex, body mass index (BMI), waist-to-hip ratio (WHR), and dietary saturated fatty acids. The association with age and BMI persisted in multivariate analyses.

A comparison of total body water measurements using whole-body magnetic resonance imaging versus tritium dilution in primates.

Standard techniques conventionally used to assess body composition have various drawbacks which include a requirement for specialized equipment and expertise not widely available, radiation exposure, extensive study time periods, and limited clinical utility. Anthropometric methods, which are more clinically feasible, also involve substantially greater calculation error. This study was designed to compare a newly developed whole-body magnetic resonance (MR) imaging technique with standard tritium dilution (THO) to measure total body water (TBW) in eight primates (Macaca fascicularis). Sedated primates underwent whole-body MR imaging (10-12 contiguous 50-mm slices) and TBW was computed using a previously validated program. After 5 days to allow for primate recovery and stabilization, TBW measurements were repeated using THO methodology. Linear regression analysis of TBWMRI (72.1 +/- 5.7% body wt) compared with TBWTHO (73.8 +/- 3.2% body wt) yielded a Pearson correlation of r = 0.8145, P = 0.02 with a mean squared error of 2.14. Whole-body MR imaging determination of TBW correlates well with THO, requires less time (20 min versus 24 hr), and does not expose the subject to radiation. This study suggests that whole-body MR imaging is an accurate technique for in vivo body composition analysis. As demonstrated by the body size of this investigational primate model, the technique maybe particularly applicable to the study of human infants.

Broad line quantitative chemical shift spectroscopy.

Proton NMR spectroscopy was applied to quantitate the measurement of total body water/fat distributions in vivo. A special MR protocol was developed to excite a thick slab of tissue and display the magnitude NMR spectrum of the collected response signal. Very short echo time TE (8 ms) and long repetition time TR (4000 ms) were used to minimize relaxation damping of the signal intensities. The spectrum was then decomposed into individual lines and proton densities of different species were calculated. Proton density information was converted into weight percentage data using stoichiometrical and physiological information. The technique was validated using phantoms that contained different mixtures of water/maize oil. A high-resolution NMR spectrum of maize oil samples was used to determine the stoichiometric information. The test results showed good agreement with the known composition of the phantom within the whole range of water content (0-100%). This method is very fast since no phase encoding of data is required. Preliminary results for monkeys show promising potential in clinical applications.

NMR spin-lattice relaxation in tissues with high concentration of paramagnetic contrast media: evaluation of water exchange rates in intact rat muscle.

High concentrations of GdDTPA in extracellular water of tissue cause the intrinsic relaxation rate of water to become greater than the coupling rate between intracellular and extracellular water compartments. The fast exchange limit is no longer valid and distinctly nonexponential spin-lattice recovery is observed. T1 relaxation recovery was characterized by a double exponential curve when striated rat muscle was immersed in a highly concentrated (110 Mm) isotonic solution of GdDTPA. When the water exchange rate through cell membranes in intact muscle tissue was calculated (using a two-compartment exchange model) and compared to similar data determined from T2 Carr-Purcell-Meiboom-Gill experiments, a significant discrepancy was found.

Pseudolayering of Gd-DTPA in the urinary bladder.

When excreted gadolinium diethylenetriaminepentaacetic acid (DTPA) collects in the bladder of a supine patient during magnetic resonance (MR) imaging, a puzzling pattern of signal intensities is noted. A gradual change in urine signal intensity with progressive addition of Gd-DTPA does not occur; instead, three sharply defined "layers" are seen both on T1- and T2-weighted images within the urine-Gd-DTPA mixture. The physical basis for this triple-layering phenomenon was investigated. A bladder phantom was constructed to reproduce the phenomenon. T1 and T2 relaxivities of urine doped with varying concentrations of Gd-DTPA were measured in vitro; measured signal intensities corresponded closely to predicted intensities. Early urine concentrations of excreted Gd-DTPA may be relatively high (10-40 mmol/L), resulting in extremely short T1 and T2 values (less than 30 msec). These extremely short relaxation times cause an artifactual pseudolayering of signal within the urine-Gd-DTPA mixture.

A new method of computing spin-lattice relaxation maps in magnetic resonance imaging using fast scanning protocols.

A new algorithm to compute spin-lattice relaxation (T1) maps in magnetic resonance imaging (MRI) by using fast imaging protocols and monitoring the magnetization evolution towards a steady state is proposed. This algorithm uses a general least-squares fit to multiple point experimental data and is thus much more precise than the standard two-point fit. Since this imaging protocol is designed to consume time comparable to that of standard clinical protocols, it has an advantage in comparison to traditional multiple point protocols, which require considerably longer scanning times. In addition to T1 maps the protocol can generate final images suitable for clinical diagnosis. Thus it is possible to generate relaxation data without considerably lengthening the total required MRI study time. The results of phantom testing of this protocol are reported.

MR flow imaging in projection through a stationary surround.

A magnetic resonance imaging technique is discussed which, by cyclic inversion of the longitudinal magnetization, produces boli of moving material with alternating sign of the magnetization. At periodic spacings along the flow direction, the signal strength from magnetization of positive sign is equal to that of negative sign. This results in a minimum in the intensity distribution. A banded intensity structure results reflecting the distribution of flow velocities across the imaged vessel. The inversion of the longitudinal magnetization causes an inherent suppression of the signal from stationary material allowing the collection of flow images in projection through a stationary surround without the need for image subtraction.

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues.

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.

Use of a paramagnetic substance, colloidal manganese sulfide, as an NMR contrast material in rats.

Paramagnetic pharmaceuticals ( magnetopharmaceuticals ) that are suitably distributed into specific organ systems or diseased sites might be clinically useful for tissue contrast enhancement in nuclear magnetic resonance images. To determine whether an insoluble magnetopharmaceutical might be useful in such service, we investigated the effect of a colloidal preparation of manganese sulfide ( MnSC ) upon liver and lung spin-lattice relaxation times (T1) in rats following intravenous administration. NMR tissue sample measurements were made at 24 MHz, ahd showed that after MnSC treatment, liver T1 values--and to a lesser extent lung T1 values--were depressed below control values. Liver manganese content (as determined by flame atomic absorption spectrophotometry) increased in proportion to the dose of MnSC , and the reciprocal of the liver T1 values also increased in proportion to the dose of MnSC .