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Mathematical analysis of arterial enhancement and optimization of bolus geometry for CT angiography using the discrete fourier transform.

PURPOSE: The goal of this work was to develop a clinically applicable mathematical algorithm to analyze and optimize individual arterial enhancement in CT angiography (CTA). METHOD: Assuming a time-invariant linear system, the discrete Fourier transform was used to calculate the transfer function of the system ("patient function") from the arterial time-attenuation response to a test bolus. The patient function was subsequently used to predict aortic enhancement in five select patients and to calculate optimized biphasic injection protocols in two of these patients undergoing CTA of the abdominal aorta. RESULTS: Arterial time-attenuation curves were accurately predicted in all patients. Optimized biphasic contrast agent injection protocols resulted in uniform aortic enhancement at the predefined level over the entire scanning period in both subjects despite markedly different contrast agent volumes and injection rates used. CONCLUSION: Fourier analysis of the time-attenuation response to a test bolus is a simple and feasible approach to optimize arterial enhancement in CTA.

Angiography↗

Contrast-enhanced magnetic resonance angiography of the iliac arteries: optimization by injection simulation.

Protocols for contrast-enhanced magnetic resonance angiography (CE-MRA) of the iliac arteries were optimized by computer simulations based on an impulse response function (IRF) of contrast agent (CA) concentration as a function of time obtained for 20 patients. Protocols with sequential, centric, and elliptical k-space coverage, different repetition rates (5 and 10 ms), and CA doses (0.1, 0.2, and 0.3 mmol/kg b.w.) were compared in terms of signal-to-noise ratio (SNR), distortion of vessel profiles, and sensitivity to timing errors. IRF-based simulations successfully characterized CA recirculation. Slow-rate CA infusions were found to achieve relatively high enhancement. In terms of SNR, there is no advantage in increasing the repetition rate. Distortion of vessel profiles is more likely in elliptic and centric k-space coverage. Protocols based on sequential k-space coverage and relatively long CA infusions proved to be particularly suited to large-FOV iliac examinations as they are relatively insensitive to timing errors.

Adult↗

Optimization of MDCT of the wrist to achieve diagnostic image quality with minimum radiation exposure.

OBJECTIVE: This study tests various acquisition and reconstruction protocols for MDCT of the wrist to determine the optimal protocol for obtaining diagnostic image quality with minimal radiation exposure. MATERIALS AND METHODS: Thirty anatomic specimens were examined with an MDCT collimation of 4.0 x 1.0 mm and 2.0 x 0.5 mm (80, 120, and 140 kV; 80, 100, 130, 160, and 200 mA; rotation time, 0.5 0.75, 1.0 sec; pitch, 1.0, 1.3, 1.5, and 2.0). Coronal images were reconstructed using a slice thickness of 0.5, 1.0, and 2.0 mm with 60% overlap. Three observers evaluated all images independently for gross and fine anatomic detail. Diagnostic confidence was tested using Shrout-Fleiss intraclass correlation coefficients. Interobserver agreement was assessed by Kappa statistics and the Kruskal-Wallis test. RESULTS: Fine anatomic detail was best presented in 0.5-mm or 1.00-mm reconstructions based on a 2.0 x 0.5 mm acquisition. A rotation time of > or = 0.75 sec resulted in fewer artifacts; a significant dose reduction was achieved with 80 kV and 100 mA at the expense of somewhat increased noise, but without significant loss of anatomic detail in bone presentation. Artifacts were tolerable with a pitch of 1.5 or less. CONCLUSION: MDCT at the described optimal settings allows significant dosage reduction without sacrificing image quality. An acquisition and reconstruction thickness of 0.5 mm results in the best depiction of anatomic detail. A reconstruction thickness of 1.0 mm with a reconstruction interval of 0.5 mm represents a good trade-off between noise and resolution when using low-dose protocols.

Aged↗

Determining the optimal timing for early arterial phase hepatic CT imaging by measuring abdominal aortic enhancement in variable contrast injection protocols.

OBJECTIVE: To find the optimal scan timing for early arterial phase hepatic CT with adequate arterial enhancement after the aortic contrast arrival. METHODS: Sixty patients were divided randomly into three groups, each of which received 2.0 mL/kg of the 300 mgI/mL contrast medium with an injection duration of 30 seconds (Group A, mean rate 3.6 mL/sec); of 25 seconds (B, 4.6 mL/sec); of 30 seconds (3.6 mL/sec) followed by a saline chaser (C). RESULTS: After the contrast arrival, aortic enhancement increased rapidly for 6-15 seconds (mean, 10 seconds) to the initial peak enhancement in all groups, and then, increased moderately to the maximum aortic enhancement over the following 19, 13, and 21 seconds, respectively. The mean maximum aortic enhancement in Group B (392 HU) and C (360 HU) were significantly higher than that in A (326 HU), respectively. The difference between the initial and maximum aortic enhancement was less than 50 HU. CONCLUSION: The optimal timing of the early arterial phase for hepatic CT arteriography is 10-15 seconds after the aortic arrival.

Adult↗

Optimized DNA extraction to improve reproducibility of short tandem repeat genotyping with highly degraded DNA as target.

The reproducibility of short tandem repeat (STR) genotyping of highly degraded DNA is often reduced due to artifacts generated during polymerase chain reaction (PCR) amplification. The frequency and amount of these artifacts are related to the quality and quantity of the DNA amplified. Consequently, the aim of this investigation was the optimization of DNA extraction to increase the reproducibility of STR genotyping of samples containing highly degraded DNA. Starting from a standard extraction protocol, systematic variation of individual parameters resulted in optimized protocols for three categories of ancient human bone material (different degrees of DNA degradation) and a consensus protocol for the extraction of a broad range of ancient DNA preservation states.

DNA↗

Linear programming optimization and a double statistical filter for protein threading protocols.

The design of scoring functions (or potentials) for threading, differentiating native-like from non-native structures with a limited computational cost, is an active field of research. We revisit two widely used families of threading potentials: the pairwise and profile models. To design optimal scoring functions we use linear programming (LP). The LP protocol makes it possible to measure the difficulty of a particular training set in conjunction with a specific form of the scoring function. Gapless threading demonstrates that pair potentials have larger prediction capacity compared with profile energies. However, alignments with gaps are easier to compute with profile potentials. We therefore search and propose a new profile model with comparable prediction capacity to contact potentials. A protocol to determine optimal energy parameters for gaps, using LP, is also presented. A statistical test, based on a combination of local and global Z-scores, is employed to filter out false-positives. Extensive tests of the new protocol are presented. The new model provides an efficient alternative for threading with pair energies, maintaining comparable accuracy. The code, databases, and a prediction server are available at http://www.tc.cornell.edu/CBIO/loopp.

Amino Acid Sequence↗

MR imaging of CNS tumors: are all contrast agents created the same?

The challenging and multiple goals and requirements of CNS tumor imaging require optimization of the CNS imaging protocols, including selection of the optimal contrast medium. There are several gadolinium compounds available for imaging the CNS, and all of these except the compound Gd-BOPTA have nearly identical profiles. The unique protein interaction of Gd-BOPTA results in double T1 and T2 relaxivity. This article summarizes the advantages of Gd-BOPTA over conventional gadolinium compounds in both conventional and functional MR imaging. The results of recent studies in adults and pediatric patients are presented and discussed. The principal conclusion of this article is that not all contrast agents approved for MR imaging of the CNS behave in the same way. The use of the high-relaxivity agent Gd-BOPTA for morphological and functional MR imaging allows improved detection and delineation of CNS lesions compared to conventional gadolinium agents. This not only permits more confident diagnoses, but also results in a substantially improved differential diagnostic process. The higher relaxivity of Gd-BOPTA helps to optimize functional MR imaging studies e.g. perfusion MR imaging and other dynamic MR imaging protocols.

Central Nervous System Neoplasms↗

Mathematical optimization of glaucoma visual field screening protocols.

There is potential for significantly shortening the time required for visual field screening protocols by a precise specification of the number, exact location, and sequence of points to be tested. Through statistical and mathematical methods, protocols have been developed for maximizing the probability of detecting at least one visual field defect in a subject who is a risk for early glaucomatous field loss. The mathematical formulation was derived in a generalized manner so that it could be applied to most kinetically or statically determined visual field screening methods.

Glaucoma↗

Optimization of a peptide-based protocol employing IL-7 for in vitro restimulation of human cytotoxic T lymphocyte precursors.

A variety of different methods for the in vitro restimulation of human cytotoxic T lymphocyte (CTL) precursors (CTLp) are in use. Our aim was to enhance the detection of circulating human CTLp in peripheral blood. We have developed a standardized and highly efficient method for restimulating CTLp. Synthetic peptides were used to restimulate cognate CTLp from peripheral blood mononuclear cells (PBMC), and effector CTL capable of lysing peptide-pulsed and virus infected targets were generated. The effects of several parameters on CTL specific for influenza A, EBV and HIV-1 were evaluated, and the optimum peptide concentration for CTL generation was established. Supplementation of initial cultures with IL-7 greatly enhanced peptide-specific lytic activity for all peptides tested and the dose-response relationship for IL-7 was delineated. A novel technique using peptide-MHC class I molecule tetramers to stain T cells bearing cognate T cell receptors permitted enumeration of antigen-specific CD8 + CTL during in vitro restimulation; IL-7 supplementation selectively expanded the population of peptide-specific CD8 + CTL. Importantly, this protocol, whilst enhancing the restimulation and lytic activity of secondary CTL, does not induce primary CTL in vitro. The improved efficiency with which CTL are generated in this system substantially enhances the sensitivity of CTL culture and the 51Cr release assay to detect low levels of CTL activity.

Antigen Presentation↗

Computed tomography of the urinary tract: optimalization of low-dose stone protocol in a clinical setting.

PURPOSE: To establish whether information would be lost if slice reconstruction thickness was increased from 3 to 5 mm, and whether this altered how difficult it was to interpret the examinations. MATERIAL AND METHODS: Twenty-three consecutive patients referred with suspected or known urinary stones were included. All examinations were performed without intravenous contrast media. The original series, with effective mAs 50, were reconstructed with slice thickness 3 and 5 mm, respectively. All demographic and examination data were removed and the series reviewed in PACS by two independent radiologists. Objective findings, i.e. number and size of stones, signs of obstruction, and evaluation of interpretation difficulty, were registered. RESULTS: Identical findings were registered in 18 of the series of 3 mm (n=23) and 19 of the series of 5 mm (n=23). In two series reconstructed with 3 mm slice thickness and in one series with 5 mm slice thickness, the observers disagreed on the presence of urinary stones. Main reasons for interpretation difficulties were given as "lack of intra-abdominal fat" and "many phleboliths in the pelvic region", but never "disturbing noise". CONCLUSION: To determine the presence and size of urinary stones at low-dose computed tomography, 5 mm reconstruction algorithm seems equal to 3 mm. Patient-related factors influence the interpretation more than image quality.

Adult↗

Optimizing gonadotrophin-releasing hormone antagonist protocols.

The introduction of the gonadotrophin-releasing hormone(GnRH) antagonists offers new potential for in vitro fertilization (IVF) clinics. Compared with GnRH agonists, the use of the GnRH antagonists significantly reduces the dose of gonadotrophin and duration of treatment required, and also reduces unwanted side-effects. Patients also tend to prefer treatment with GnRH antagonists compared with agonists. The GnRH antagonists are useful in both good and poor responders, and there is some flexibility in treatment protocols. A single dose of GnRH antagonist may be used in patients who do not want or require more aggressive stimulation. Promising data indicate advantages of GnRH antagonists in terms of reduced incidence of ovarian hyperstimulation syndrome and reduced impairment of luteal function. It is anticipated that, as a result of further development of treatment protocols, pregnancy rates with the GnRH antagonists will become at least equivalent to those achieved with GnRH agonist protocols.

Clinical Trials, Phase III as Topic↗

Upper extremity functional assessment after anterior spinal fusion via thoracotomy for adolescent idiopathic scoliosis: prospective study of twenty-five patients.

STUDY DESIGN: A prospective review of upper extremity function in 25 patients after anterior thoracotomy for instrumentation and fusion of thoracic adolescent idiopathic scoliosis was conducted. OBJECTIVE: To assess the effects of anterior spinal fusion with open thoracotomy on upper extremity function. SUMMARY OF BACKGROUND DATA: The treatment of idiopathic scoliosis through anterior thoracotomy and spinal fusion using instrumentation is a new method for correcting and stabilizing patients with major thoracic and thoracolumbar curves. No studies have assessed the functional outcome for the upper extremities after anterior open thoracotomy that involves splitting through the latissimus dorsi and serratus anterior muscles. METHODS: For this study, 25 adolescent patients with idiopathic scoliosis treated surgically were examined over a 3-year period. The average patient age was 15 years and 3 months, with a range of 11 years and 11 months to 20 years and 9 months. Preoperative activities of daily living, active range of motion, and strength were recorded by an independent occupational therapist (L.P.) for both upper extremities. Postoperative measurements were assessed at 1, 3, 6, 12, and 24 months. All the patients underwent a right thoracotomy with ribs used for autograft. The left upper extremity served as the control limb. No patients had associated anomalies or previous upper extremity surgery. All the patients underwent an upper extremity postoperative stretching and strengthening protocol. RESULTS: At 1 month, 35% of the patients had some difficulty with activities of daily living, primarily in tying their shoes and cutting meat with a knife during meals (P = 0.03). However, by 3 months, all the patients could equivocally and independently perform activities of daily living: dressing, bathing, grooming, attending to hygiene, and feeding (P = 1). Full active range of motion in their upper extremities and shoulder was achieved in all the patients by 1 month (P = 1). All 25 patients had regained normal, bilaterally symmetric strength by 3 months (P = 0.25). No postoperative complications occurred. CONCLUSIONS: Patients undergoing anterior spinal fusion with instrumentation after open thoracotomy can expect to regain full function of the ipsilateral upper extremity in terms of strength, active range of motion, and activities of daily living within 3 months. Compliance with a structured postoperative flexibility and strengthening protocol is recommended to optimize functional outcomes. A novel rehabilitation protocol for the upper extremities is presented.

Activities of Daily Living↗

Detection and enumeration of bacteria in soil by direct DNA extraction and polymerase chain reaction.

In order to develop a rapid and specific detection test for bacteria in soil, we improved a method based on the polymerase chain reaction (PCR). Each step of the protocol, including direct lysis of cells, DNA purification, and PCR amplification, was optimized. To increase the efficiency of lysis, a step particularly critical for some microorganisms which resist classical techniques, we used small soil samples (100 mg) and various lytic treatments, including sonication, microwave heating, and thermal shocks. Purification of nucleic acids was achieved by passage through up to three Elutip d columns. Finally, PCR amplifications were optimized via biphasic protocols using booster conditions, lower denaturation temperatures, and addition of formamide. Two microorganisms were used as models: Agrobacterium tumefaciens, which is naturally absent from the soil used and was inoculated to calibrate the validity of the protocol, and Frankia spp., an actinomycete indigenous to the soil used. Specific primers were characterized either in the plasmid-borne vir genes for A. tumefaciens or in the variable regions of the 16S ribosomal gene for Frankia spp. Specific detection of the inoculated A. tumefaciens strain was routinely obtained when inocula ranged from 10(7) to 10(3) cells. Moreover, the strong correlation we observed between the size of the inocula and the results of the PCR reactions permitted assessment of the validity of the protocol in enumerating the number of microbial cells present in a soil sample. This allowed us to estimate the indigenous population of Frankia spp. at 0.2 x 10(5) genomes (i.e., amplifiable target sequences) per g of soil.

Agrobacterium tumefaciens↗

Peripheral pulmonary arteries: optimization of the spiral CT acquisition protocol.

PURPOSE: To analyze the influence of collimation on identification of segmental and subsegmental pulmonary arteries on spiral computed tomographic (CT) scans. MATERIAL AND METHODS: Contrast material-enhanced spiral CT scans were retrospectively analyzed. Patients in group A (n = 20) underwent CT with 3-mm collimation, 1.00 second per revolution, and pitch of 1.7; those in group B (n = 20) underwent CT with 2-mm collimation, 0.75 second per revolution, and pitch of 2.0. A total of 800 segmental (20 arteries per patient) and 1,600 subsegmental (40 arteries per patient) arteries were assessed. RESULTS: The mean number of analyzable segmental arteries per patient was greater in group B patients (18.6 of 20.0 [93%]) than that in group A patients (17.0 of 20.0 [85%]) (P < .001). The mean number of analyzable subsegmental arteries per patient was greater in group B patients (24.6 of 40.0 [61%]) than that in group A patients (14.8 of 40.0 [37%]) (P < .0001). Frequency of identification on CT scans of 13 of the 40 subsegmental arteries was improved in group B compared with group A patients (P < .0001). CONCLUSION: Spiral CT with 2-mm collimation at 0.75 second per revolution enables marked improvement in the analysis of segmental and subsegmental pulmonary arteries.

Adult↗

Optimization of an automated DNA purification protocol for neonatal screening.

CONTEXT: Collection of blood from newborns is a standard clinical procedure used for genetic screening. Typically, blood from a heel prick is absorbed onto standard collection paper and dried before analysis of metabolites, proteins, hormones, and more recently DNA. OBJECTIVE: To evaluate strategies to purify DNA for use with automated workstations. DESIGN: Two factors were used to evaluate several DNA purification protocols: residual heme contamination and amplification yield. The protocol that produced DNA with the lowest heme content and the highest amplification yield was selected. In combination with those two performance factors, the protocol with the fewest number of steps was chosen to reduce reagent use and processing time. SETTING: Industrial research and development laboratory. RESULTS: Robust amplification of DNA isolated from dried blood spots was demonstrated using both fluorescence and agarose gel-based detection methods. In addition, the samples had consistent DNA volumes and had no detectable cross-contamination. Suggested instrument settings, equipment, and supplies were included for automated processing of DNA from dried blood spots. CONCLUSION: A 4-step DNA processing protocol was developed for dried blood spots. The protocol could be performed in either a manual or automated format, making it possible to process hundreds of samples in 1 day.

Blood Chemical Analysis↗

Effect of peripheral biopsies in maximising early prostate cancer detection in 8-, 10- or 12-core biopsy regimens.

OBJECTIVE: To assess the cancer detection rate per individual core biopsy in a 12-core protocol and develop an optimal biopsy regimen for detecting early prostate cancer. PATIENTS AND METHODS: The study included 445 new patients who had a 12-core transrectal ultrasonography (TRUS)-guided prostatic biopsy over a 40-month period. The 12- core biopsy protocol included parasagittal sextant and six peripheral biopsies. The cancer detection rate per individual core was evaluated to give an optimal biopsy protocol. RESULTS: Prostate cancer was detected in 142 patients (31.9%). Parasagittal sextant biopsy would have failed to detect 40 (28.2%) of the cancers. Among the various possible biopsy protocols, the optimum 10-core biopsy strategy excluding the parasagittal mid-zone biopsies from the 12-core protocol achieved a cancer detection rate of 98.6%. CONCLUSION: The cancer detection rate increased from 71.8% for parasagittal sextant biopsies to 88.7% by adding peripheral basal biopsies (8-biopsy protocol); 98.6% of cancers in the series would have been detected with a 10-biopsy strategy omitting the parasagittal mid-zone biopsies. Thus we recommend a 10-core protocol incorporating six peripheral biopsies in patients with elevated age- specific prostate-specific antigen levels (2.6-10.0 ng/mL) for maximising cancer detection.

Adult↗

Immunohistochemical detection of thrombospondin-1 in formalin-fixed, paraffin-embedded tissue.

Thrombospondin-1 (TSP) is a 450-KD glycoprotein that was initially discovered in the platelet alpha-granule. It now appears that TSP is intimately involved in the regulation of a variety of cellular functions and cell-to-cell interactions. Recently, it has been demonstrated that TSP functions as a p53-dependent inhibitor of angiogenesis in cultured fibroblasts from Li-Fraumeni patients and therefore may be an important factor involved with tumor invasion and metastasis. It has previously been demonstrated that TSP can be detected in frozen tissue sections by immunohistochemical methods. Our objective in this study was to determine the optimal antigen retrieval (AR) protocol for detection of TSP in formalin-fixed, paraffin-embedded tissue by using tissue sections from patients with invasive transitional cell carcinoma of the bladder. The optimal AR protocol was determined utilizing a variety of heating conditions and antigen retrieval buffers. Our results demonstrate that TSP can be reliably detected in paraffin-embedded tissue by immunohistochemical techniques that utilize AR with high-temperature microwave heating and a low-pH Tris-HCI buffer. The importance of this method is that it allows the reliable detection of TSP in archival tissue. This should facilitate further investigation into TSP's role in the regulation of cellular processes, including its influence on tumor angiogenesis and metastasis.

Carcinoma, Transitional Cell↗

Importance in optimization of multi-slice computed tomography scan protocols.

This paper reviews the reasons why multi-slice CT scanners may give patients higher dose than their single-slice predecessors and discusses the type of optimization of multi-slice scan protocols that may be undertaken to keep patient doses to acceptable levels without compromising image quality. It also provides estimates of patient effective dose values and dose length products for typical procedures and briefly discusses the implication that these dose values have for the induction of possible stochastic effects.

Humans↗