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Technical aspects of myocardial SPECT imaging with technetium-99m sestamibi.

Most reports to date using single photon emission computed tomography (SPECT) with technetium-99m (Tc-99m) sestamibi have used acquisition parameters that were optimized for thallium-201. To fully utilize the superior imaging characteristics of Tc-99m sestamibi, there is a need to optimize the technical aspects of SPECT imaging for this agent. Performance can be enhanced through the careful selection of optimal radiopharmaceutical doses, imaging sequences, acquisition parameters, reconstruction filters, perfusion quantification methods and multidimensional methods for visualizing perfusion distribution. The current report describes theoretical considerations, phantom studies and preliminary patient results that have led to optimized protocols, developed at Emory University and Cedars-Sinai Medical Center, for same-day rest-stress studies, given existing instrumentation and recommended dose limits. The optimizations were designed to fit a low-dose-high-dose rest-stress same-day imaging protocol. A principal change in the acquisition parameters compared with previous Tc-99m sestamibi protocols is the use of a high-resolution collimator. The approach is being developed in both prone and supine positions. A new method for extracting a 3-dimensional myocardial count distribution has been developed that uses spherical coordinates to sample the apical region and cylindrical coordinates to sample the rest of the myocardium. New methods for visualizing the myocardial distribution in multiple dimensions are also described, with improved 2-dimensional, as well as 3- and 4-dimensional (3 dimensions plus time) displays. In the improved 2-dimensional display, distance-weighted and volume-weighted polar maps are used that appear to significantly improve the representation of defect location and defect extent, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Graphics↗

Controlled release of plasmid DNA from biodegradable scaffolds fabricated using a thermally-induced phase-separation method.

Highly porous poly(D,L-lactic-co-glycolic acid) (PLGA) scaffolds were fabricated by a thermally-induced phase-separation (TIPS) method to deliver plasmid DNA in a controlled manner. A variety of TIPS parameters directly affecting pore structures and their interconnectivities of the scaffold, such as polymer concentration, solvent/non-solvent ratio, quenching methods and annealing time, were systematically examined to explore their effects on sustained release behaviors of plasmid DNA. Plasmid DNA was directly loaded into the inner pore region of the scaffold during the TIPS process. By optimizing the parameters, PLGA scaffolds releasing plasmid DNA over 21 days were successfully fabricated. DNA release profiles were mainly affected by the pore structures and their interconnectivities of the scaffolds. Plasmid DNA released from the scaffolds fully maintained its structural integrity and showed comparable transfection efficiency to native plasmid DNA. These biodegradable polymeric scaffolds capable of sustained DNA release can be potentially applied for various tissue engineering purposes requiring a combined gene delivery strategy.

Absorbable Implants↗

A theoretical model for the myogenic response based on the length-tension characteristics of vascular smooth muscle.

OBJECTIVE: A theoretical model is developed to describe the myogenic response of resistance vessels to changes in intravascular pressure, based on a consideration of the active and passive length-tension characteristics of vascular smooth muscle (VSM). The dependence of model parameters on vessel diameter is examined. METHODS: The vessel wall is represented mechanically as a nonlinear passive component in parallel with an active contractile component. The level of VSM tone is assumed to have a sigmoidal dependence on circumferential wall tension or stress. Model parameters are optimized for each of 18 independent experimental data sets previously obtained using pressure or wire myograph systems. RESULTS: Close fits between model predictions and experimental data are found in each case. An alternative formulation in which VSM tone depends on circumferential wall stress is found also to be consistent with available data. Significant trends in model parameters as a function of diameter are found. CONCLUSIONS: The results support the hypothesis that circumferential tension or stress in the wall provides the signal for myogenic responses. The model provides a basis for simulating steady-state myogenic responses in vascular networks containing a range of vessel diameters.

Animals↗

P1 Shake-and-Bake: can success be guaranteed?

The multi-trial direct-methods procedure known as Shake-and-Bake has been applied to three small proteins (alpha-1 peptide, vancomycin and lysozyme) that crystallize in space group P1. Phase refinement was accomplished through parameter-shift optimization using both the cosine and exponential forms of the minimal function. By extending error-free data to sufficiently high resolution, 100% convergence of trial structures to solution could be achieved in all three cases by using the exponential minimal function and a shift angle in the range 130-150 degrees. These results suggest optimum parameters for other P1 structures and emphasize the importance of collecting data to the highest possible resolution.

Algorithms↗

Treatment parameters for selective occlusion of experimental corneal neovascularization by photodynamic therapy using a water soluble photosensitizer, ATX-S10(Na).

Time dependent change of an accumulation of an amphiphilic photosensitizer, ATX-S10(Na) on rabbit corneal neovascularization (CoNV) was evaluated by angiography using ATX-S10(Na) as a fluorescent dye on three rabbits. The angiography showed that the dye accumulated on CoNV 3-5 hr after dye injection when the dye in the iris was minimum. The results suggested 3-5 hr after might be the optimal time to start photodynamic therapy (PDT) to occlude CoNV selectively without damage to the surrounding normal tissue such as the iris. Then the optimal treatment parameters in PDT using ATX-S10(Na) for selective occlusion of the CoNV were investigated on rabbit eyes. PDT was performed with two different time intervals between dye injection and laser irradiation of a diode laser (670 nm), different laser doses and three different dye doses on 21 animals. PDT performed immediately after dye injection selectively occluded CoNV with laser irradiations from 30.6 to 38.2 J cm(-2)and a 2 mg kg(-1)dose of ATX-S10(Na), as well as with 15.3 J cm(-2)and a 6 mg kg(-1)dose. PDT performed 4 hr after dye injection with 107.0-152.8 J cm(-2)and a 6 mg kg(-1)dose, as well as with 38.2-53.5 J cm(-2)and a 12 mg kg(-1)dose was also effective. Although PDT performed either immediately or 4 hr after ATX-S10(Na) injection selectively occluded CoNV, the width of the optimal range of radiant exposures seemed wider in PDT performed 4 hr after dye injection. It is supposed that this result is associated with the difference of dye accumulation between in CoNV and in normal tissue as shown by the present angiographical findings.

Animals↗

Assessing and optimizing the performance of a phase-shifting interferometer capable of measuring the complex index of refraction and the surface profile of a test surface.

A novel interferometer based upon a conventional phase-shifting design is further investigated. This interferometer is capable of measuring both the real and imaginary parts of the complex index of refraction and the surface profile of a test surface. Maximum-likelihood estimation theory is shown to be an effective means of extracting the three parameters of interest from the measured data. Cramér-Rao lower bounds are introduced as a means of quantitatively assessing the performance of the system. Furthermore, it is shown that as the design parameters are optimized, the results approach the theoretical performance limit. We conclude by developing the underlying theory behind the relationship of the complex-index-of-refraction estimates to the surface-profile estimate.

Equipment Design↗

Design of experiments for the precise estimation of dose-response parameters: the Hill equation.

Optimal experimental designs were evaluated for the precise estimation of parameters of the Hill model. The optimally effective designs were obtained by using the criterion of D-optimization. For the Hill model, optimal designs replicate 3 sampling points. These points were shown to be quite sensitive to the behavior of the experimental error. Since an investigator is often uncertain about error conditions in biological studies, a practical approach would use the sampling scheme calculated for an intermediate error condition. Thus, if the behavior of error variances is not known, precise parameters of the Hill model are obtained by choosing concentrations which yield fractional responses (responses divided by their asymptotic, maximum value) of 0.086, 0.581 and 1.0. When experimental constraints limit the maximum attainable concentration and response, all design points are lowered. Appropriate designs can be constructed based on the design which is optimal when constraints result in a maximum attainable fractional response of 0.5. The optimal designs were found to be robust when the parameter values assumed by the investigator did not equal their true values. The estimating efficiencies obtained by using two frequently applied designs were assessed. Uniformly spaced concentrations yielded imprecise parameters. Six-point, geometrically spaced designs gave generally good results. However, their estimating efficiency was generally exceeded by the recommended sampling schemes even in the presence of uncertainty about error conditions. The method exemplified in this paper can be used for other models.

Dose-Response Relationship, Drug↗

Improvement of brain lesion detection at 0.1 T by simultaneous use of Gd-DTPA and magnetization transfer imaging.

Imaging parameters were optimized at 0.1 T to improve contrast-to-noise ratios (CNR) when combining magnetization transfer (MT) imaging and the use of paramagnetic contrast medium. This was accomplished by imaging a phantom containing serial concentrations of Gd-DTPA in cross-linked bovine serum albumin. With the use of simulations, the dependence of CNR on imaging parameters was studied. Conventional and MT images were obtained from 10 brain tumor patients with single and triple doses of Gd-DTPA. Simulations demonstrated the importance of TR in postcontrast sequences. The CNR in MT images is less sensitive to TR than in conventional images. A significant CNR improvement caused by MT remains at longer TR when there is no contrast enhancement without MT. The clinical results indicate that a single dose of Gd-DTPA combined with MT cannot replace imaging with a triple dose. However, MT significantly improved the CNR after single and triple Gd-DTPA-doses on T1-weighted and proton-density images.

Adult↗

[Evaluation of cyclodextrin inclusion of the volatile components in compound traditional Chinese medicine].

OBJECTIVE: To study the factors affecting cyclodextrin (CD) inclusion of the volatile components in compound traditional Chinese medicines and evaluate the stability of the inclusion compound. METHODS: This study took Gengnian compound as an example to examine the factors affecting the inclusion process according to the inclusion compound utilization ratio. Orthogonal design method was employed optimize the parameters in the inclusion process. The moisture absorption rate of the beta-CD inclusion compound was determined in different humidity and Q10 was used to predict its. RESULTS: The inclusion method, inclusion compound dosage, temperature, inclusion time, and the drying method could all obviously influence the inclusion process. The results of orthogonal design study showed that the optimal beta-CD inclusion of Gengnian compound volatile components could be achieved by adding 8-fold volume of beta-CD and stirring for 3 h at room temperature. Stability experiment showed that the humility did not significantly influence the inclusion compound, which can be stable for 1.26 years. CONCLUSION: This study comprehensively examines the factors affecting the inclusion process and the stability of the inclusion compound, and provides experimental basis for application and study of the inclusion technology.

Drug Combinations↗

Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure.

An improved dynamic programming algorithm is reported for RNA secondary structure prediction by free energy minimization. Thermodynamic parameters for the stabilities of secondary structure motifs are revised to include expanded sequence dependence as revealed by recent experiments. Additional algorithmic improvements include reduced search time and storage for multibranch loop free energies and improved imposition of folding constraints. An extended database of 151,503 nt in 955 structures? determined by comparative sequence analysis was assembled to allow optimization of parameters not based on experiments and to test the accuracy of the algorithm. On average, the predicted lowest free energy structure contains 73 % of known base-pairs when domains of fewer than 700 nt are folded; this compares with 64 % accuracy for previous versions of the algorithm and parameters. For a given sequence, a set of 750 generated structures contains one structure that, on average, has 86 % of known base-pairs. Experimental constraints, derived from enzymatic and flavin mononucleotide cleavage, improve the accuracy of structure predictions.

Algorithms↗

Design of methanol Feed control in Pichia pastoris fermentations based upon a growth model.

The methylotrophic yeast Pichia pastoris is an effective system for recombinant protein productions that utilizes methanol as an inducer, and also as carbon and energy source for a Mut(+) (methanol utilization plus) strain. Pichia fermentation is conducted in a fed-batch mode to obtain a high cell density for a high productivity. An accurate methanol control is required in the methanol fed-batch phase (induction phase) in the fermentation. A simple "on-off" control strategy is inadequate for precise control of methanol concentrations in the fermentor. In this paper we employed a PID (proportional, integral and derivative) control system for the methanol concentration control and designed the PID controller settings on the basis of a Pichia growth model. The closed-loop system was built with four components: PID controller, methanol feed pump, fermentation process, and methanol sensor. First, modeling and transfer functions for all components were derived, followed by frequency response analysis, a powerful method for calculating the optimal PID parameters K(c) (controller gain), tau(I) (controller integral time constant), and tau(D) (controller derivative time constant). Bode stability criteria were used to develop the stability diagram for evaluating the designed settings during the entire methanol fed-batch phase. Fermentations were conducted using four Pichia strains, each expressing a different protein, to verify the control performance with optimal PID settings. The results showed that the methanol concentration matched the set point very well with only small overshoot when the set point was switched, which indicated that a very good control performance was achieved. The method developed in this paper is robust and can serve as a framework for the design of other PID feedback control systems in biological processes.

Bioreactors↗

Determination of sugar structures in solution from residual dipolar coupling constants: methodology and application to methyl beta-D-xylopyranoside.

We have developed methodology for the determination of solution structures of small molecules from residual dipolar coupling constants measured in dilute liquid crystals. The power of the new technique is demonstrated by the determination of the structure of methyl beta-d-xylopyranoside (I) in solution. An oriented sample of I was prepared using a mixture of C(12)E(5) and hexanol in D(2)O. Thirty residual dipolar coupling constants, ranging from -6.44 to 4.99 Hz, were measured using intensity-based J-modulated NMR techniques. These include 15 D(HH), 4 (1)D(CH), and 11 (n)D(CH) coupling constants. The accuracy of the dipolar coupling constants is estimated to be < +/- 0.02 Hz. New constant-time HMBC NMR experiments were developed for the measurement of (n)D(CH) coupling constants, the use of which was crucial for the successful structure determination of I, as they allowed us to increase the number of fitted parameters. The structure of I was refined using a model in which the directly bonded interatom distances were fixed at their ab initio values, while 16 geometrical and 5 order parameters were optimized. These included 2 CCC and 6 CCH angles, and 2 CCCC and 6 CCCH dihedral angles. Vibrationally averaged dipolar coupling constants were used during the refinement. The refined solution structure of I is very similar to that obtained by ab initio calculations, with 11 bond and dihedral angles differing by 0.8 degrees or less and the remaining 5 parameters differing by up to 3.3 degrees . Comparison with the neutron diffraction structure showed larger differences attributable to crystal packing effects. Reducing the degree of order by using dilute liquid crystalline media in combination with precise measurement of small residual dipolar coupling constants, as shown here, is a way of overcoming the limitation of strongly orienting liquid crystals associated with the complexity of (1)H NMR spectra for molecules with more than 12 protons.

Carbohydrate Conformation↗

Volumetric cartilage measurements of porcine knee at 1.5-T and 3.0-T MR imaging: evaluation of precision and accuracy.

PURPOSE: To compare the precision and accuracy of 3.0-T and 1.5-T magnetic resonance (MR) imaging in the quantification of cartilage volume by using direct volumetric measurements as a reference standard. MATERIALS AND METHODS: The local animal experimentation committee did not require its approval for this study. Porcine knees were obtained from an abattoir. These specimens were used to optimize imaging parameters regarding effective signal-to-noise ratio (SNRE) and contrast-to-noise ratio (CNRE) for a fat-saturated spoiled gradient-recalled acquisition in the steady state (SPGR) sequence, a water excitation SPGR sequence, and a fast spin-echo sequence at 3.0 T and a fat-saturated SPGR sequence at 1.5 T. By using the optimized sequences, 18 specimens were imaged in less than 6 minutes per sequence. A fivefold repetition of measurements of four specimens was performed for precision analysis. Cartilage was segmented by using semiautomatic software to calculate the volume. After imaging, the cartilage was scraped off and the volume was measured directly by using a saline-displacement method to calculate accuracy. Precision and accuracy errors were calculated as the root-mean-squares of the single errors per specimen. RESULTS: SNRE and CNRE values, respectively, were highest for the water excitation sequence at 3.0 T (1.81 sec(-1/2) and 1.27 sec(-1/2)), followed by the fat-saturated SPGR sequence (1.52 sec(-1/2) and 1.07 sec(-1/2)). The fast spin-echo sequence and the fat-saturated SPGR sequence at 1.5 T had lower SNR(E) (1.27 sec(-1/2) and 0.59 sec(-1/2), respectively). Accuracy error for MR-based volume calculation at the femur was 5.0%, 3.0%, 21%, and 16% for the water excitation, fat-saturated SPGR, and fast spin-echo sequences at 3.0 T and the fat-saturated SPGR sequence at 1.5 T, respectively. CONCLUSION: MR imaging at 3.0 T was shown in our study to better quantify cartilage volume. SNRE and CNRE were substantially improved, resulting in significantly higher accuracy in determining cartilage volume.

Animals↗

Probabilistic linkage of large public health data files.

Probabilistic linkage technology makes it feasible and efficient to link large public health databases in a statistically justifiable manner. The problem addressed by the methodology is that of matching two files of individual data under conditions of uncertainty. Each field is subject to error which is measured by the probability that the field agrees given a record pair matches (called the m probability) and probabilities of chance agreement of its value states (called the u probability). Fellegi and Sunter pioneered record linkage theory. Advances in methodology include use of an EM algorithm for parameter estimation, optimization of matches by means of a linear sum assignment program, and more recently, a probability model that addresses both m and u probabilities for all value states of a field. This provides a means for obtaining greater precision from non-uniformly distributed fields, without the theoretical complications arising from frequency-based matching alone. The model includes an iterative parameter estimation procedure that is more robust than pre-match estimation techniques. The methodology was originally developed and tested by the author at the U.S. Census Bureau for census undercount estimation. The more recent advances and a new generalized software system were tested and validated by linking highway crashes to Emergency Medical Service (EMS) reports and to hospital admission records for the National Highway Traffic Safety Administration (NHTSA).

Adult↗

Calculation of cranial nerve complication probability for acoustic neuroma radiosurgery.

PURPOSE: Estimations of complications from stereotactic radiosurgery usually rely simply on dose-volume or dose-diameter isoeffect curves. Due to the sparse clinical data available, these curves have typically not considered the target location in the brain, target histology, or treatment plan conformality as parameters in the calculation. In this study, a predictive model was generated to estimate the probability of cranial neuropathies as a result of acoustic schwannoma radiosurgery. METHODS AND MATERIALS: The dose-volume histogram reduction scheme was used to calculate the normal tissue complication probability (NTCP) from brainstem dose-volume histograms. The model's fitting parameters were optimized to provide the best fit to the observed complication data for acoustic neuroma patients treated with stereotactic radiosurgery at the University of Florida. The calculation was then applied to the remainder of the patients in the database. RESULTS: The best fit to our clinical data was obtained using n = 0.04, m = 0.15, and alpha/beta = 2.1 Gy(-1). Although the fitting parameter m is relatively consistent with ranges found in the literature, both the volume parameter, n, and alpha/beta are much smaller than the values quoted in the literature. The fit to our clinical data indicates that brainstem, or possibly a specific portion of the brainstem, is more radiosensitive than the parameters in the literature indicate, and that there is very little volume effect; in other words, irradiation of a small fraction of the brainstem yields NTCPs that are nearly as high as those calculated for entire volume irradiation. These new fitting parameters are specific to acoustic neuroma radiosurgery, and the small volume effect that we observe may be an artifact of the fixed relationship of acoustic tumors to specific regions of the brainstem. Applying the model to our patient database, we calculate an average NTCP of 7.2% for patients who had no cranial nerve complications, and the average NTCP for was 66% for patients who sustained a cranial neuropathy. For the entire patient population, the actual percentage of patients suffering either facial or trigeminal neuropathy was 14.7%, whereas the calculated average NTCP was 14.8%. DISCUSSION: NTCP calculations using brainstem dose-volume histograms can be used to estimate the rate of cranial neuropathies from acoustic neuroma radiosurgery. More clinical data and further study will lead to refinement of the model with time.

Brain Stem↗

A field survey on the annoyance caused by sounds from large firearms and road traffic.

Subjective reactions to artillery sounds were determined for over 400 respondents divided among 17 different residential areas. Also, for the same respondents, the subjective effects of road-traffic sounds were determined enabling a comprehensive comparison of the dose-response relations. For the sake of comparison with other field surveys, the noise dose for the shooting sounds was, among other things, expressed as the yearly average C-weighted day-night level (CDNL) and that for the road-traffic sounds was expressed as the A-weighted day-night level (ADNL). Similarly, for both sound types the community response was expressed as the percentage of respondents being "highly annoyed." From the comparison of the two dose-response relationships it could be concluded that for numerically equal day-night levels, the artillery sounds were more annoying than the road-traffic sounds. Overall, the difference was equivalent to the change in annoyance produced by a 5-dB shift in the yearly average day-night levels of the sounds. With equal day-night levels for "downwind" conditions, the artillery and road-traffic sounds were equally annoying. Results from the present highly controlled field survey provided a new opportunity to optimize the parameter values in Schomer's rating procedure y = (1/beta)(LCE-PNSE) + PNSE, in which the noise exposure for impulsive sounds (y) is expressed as the A-weighted SEL of equally annoying vehicle sounds. PNSE represents the point at which the impulsive and vehicle sounds with numerically equal levels are also equally annoying. With PNSE fixed at 103 dB, an optimal solution was found with slope beta set to 1.3. With the previously recommended slope beta = 0.67, the rating sound level for artillery sounds would be underestimated by almost 12 dB.

Adult↗

Short TE MR microscopy: accurate measurement and zonal differentiation of normal hyaline cartilage.

The purpose of this study was to use MR imaging to accurately measure the thickness of hyaline cartilage and determine the MR contrast parameters for differentiation of cartilage zones in normal human cartilage samples. Cartilage samples were examined using three dimensional spin-echo MR microscopy at 9.4 T with a voxel size of 31 x 31 x 300 microns. Effects of T2 signal loss, susceptibility, and partial volume on measured thickness of cartilage were investigated. Thickness measurements were obtained on corresponding histological sections for comparison. Optimal contrast parameters for delineation of cartilage zones were evaluated using magnetization transfer, inversion recover, T1, and T2 contrast. T2 relaxation losses were identified as the primary source of discrepancy between the measured thickness of cortical bone and hyaline cartilage. Good contrast for zonal differentiation was obtained using T1 weighting. We conclude that images obtained using short TE MR microscopy can be used to accurately measure cartilage and bone thickness in human specimens, and can demonstrate zones within normal cartilage.

Bone and Bones↗

Semiquantitative analysis of SPECT images using 99Tc(m) -HMPAO in the treatment of brain perfusion after the attenuation correction by the Chang method and the application of the Butterworth filter.

The aim of this work was to optimize the parameters for semiquantitative analysis with regard to the average number of counts per pixel in tomographic projections. The analysed studies were divided into three groups, proportionally, to average the counts per pixel. The analysis of results proved the dependence (P<0.05) between the average geometric contrast of images with the maximum counts per pixel higher than 500, reconstructed with the cut-off frequency fc=0.50fn, and the standard image. Also, the same dependence was found between the group with an average of 200 counts per pixel and the standard image at the cut-off frequency fc=0.40fn. The analysis of the attenuation coefficient, c, showed significant differences. The attenuation coefficient c=0.12 cm-1 as accepted for further studies. Optimization of the matrix order of interpolation filter proved increasing of contrast with decreasing size of the matrix. In conclusion, according to the average number of counts per pixel in a projection the parameters of image reconstruction, particularly the cut-off frequency fc of the Butterworth filter, should be changed. Additionally, an attenuation correction with coefficient c=0.12 cm-1 and interpolation with matrix size equal 7x7 should be applied.

Brain↗