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Biomedical subjects

Thomas L Toth

Publications and source records attributed to Thomas L Toth.

At least 19 recordsLinked to original sources

Progressive elimination of microinjected trehalose during mouse embryonic development.

Recently, sugars such as trehalose have been introduced into mammalian cells by overcoming the permeability barrier of cell membranes, and have provided improved tolerance against stresses associated with freezing and drying. However, the fate of the intracellular sugars has remained an open question. To address this issue, mouse oocytes were microinjected with 0.1 mol/l trehalose, and intracellular trehalose and glucose concentrations were determined during embryonic development using a high performance liquid chromatography and pulsed amperometric detection protocol. Trehalose was not detected in non-injected controls at any stage of development. In the microinjection group, the amount of intracellular trehalose progressively decreased as embryos developed. There was a corresponding increase in intracellular glucose concentration at the two-cell stage, suggesting cleavage of trehalose to two glucose molecules. In summary, this study presents a simple, highly sensitive protocol to determine intracellular sugars. The data reveal rapid elimination of microinjected trehalose during embryonic development. These findings have implications for designing osmolarity-optimized culture media for sugar-injected oocytes.

Animals↗

Chest CT performed with z-axis modulation: scanning protocol and radiation dose.

Institutional review board approval of the study protocol and waiver of informed consent were obtained. This study was compliant with the Health Insurance Portability and Accountability Act. The purpose of this study was to retrospectively assess the scanning protocol and radiation dose associated with z-axis automatic tube current modulation in multi-detector row CT scanning of the chest. Fifty-three patients (mean age, 54 years; age range, 26-77 years; 25 men, 28 women) underwent 16-detector row chest CT with z-axis modulation and noise indexes of 10.0, 12.5, and 15.0 HU. Two radiologists independently compared images acquired with z-axis modulation and fixed tube current (180-300 mA) techniques for image noise, diagnostic acceptability, and depiction of peripheral bronchovascular markings. Tube current-time product was calculated for each study. There was good interobserver agreement between the two readers (kappa = 0.72). Compared with the fixed tube current technique, z-axis modulation provides acceptable image noise for chest CT, with an 18% and 26% reduction in tube current-time product at 10.0- and 12.5-HU noise indexes, respectively.

Adult↗

Do metallic endoprostheses increase radiation dose associated with automatic tube-current modulation in abdominal-pelvic MDCT? A phantom and patient study.

OBJECTIVE: Our objective was to assess the effect of orthopedic metallic prostheses on radiation dose associated with MDCT using z-axis automatic tube-current modulation and a fixed tube current in a phantom and patient study. CONCLUSION: Z-modulation is associated with a 34.1% increase in the mean tube current-time product and no change in the extent of streak artifacts in patients with a metallic prosthesis, compared with patients without a prosthesis. However, compared with the fixed-tube-current technique, z-modulation is associated with a 28.9% decrease in the mean tube current-time product.

Adult↗

Techniques and applications of automatic tube current modulation for CT.

Introduction of slip-ring technology with subsequent development of single- and multi-detector row helical computed tomographic (CT) scanners have expanded the applications of CT, leading to a substantial increase in the number of CT examinations being performed. Owing to concerns about the resultant increase in associated radiation dose, many technical innovations have been introduced. One such innovation is automatic tube current modulation. The purpose of automatic tube current modulation is to maintain constant image quality regardless of patient attenuation characteristics, thus allowing radiation dose to patients to be reduced. This review discusses the principles, clinical use, and limitations of different automatic tube current modulation techniques.

Equipment Design↗

Strategies for CT radiation dose optimization.

Recent technologic advances have markedly enhanced the clinical applications of computed tomography (CT). While the benefits of CT exceed the harmful effects of radiation exposure in patients, increasing radiation doses to the population have raised a compelling case for reduction of radiation exposure from CT. Strategies for radiation dose reduction are difficult to devise, however, because of a lack of guidelines regarding CT examination and scanning techniques. Various methods and strategies based on individual patient attributes and CT technology have been explored for dose optimization. It is the purpose of this review article to outline basic principles of CT radiation exposure and emphasize the need for CT radiation dose optimization based on modification of scanning parameters and application of recent technologic innovations.

Adult↗

Use of sugars in cryopreserving human oocytes.

In the last 20 years, a worldwide effort to cryopreserve oocytes has resulted in 40 infants and approximately 50 ongoing pregnancies being reported. While the ability to freeze human embryos has become a standard of practice in assisted reproductive technologies, obtaining reliable techniques for oocyte cryopreservation has been more difficult. The unique properties of the mature oocyte, such as the meiotic stage with sensitive spindle structure as well as the large cell volume, are responsible for the limited success obtained to date. There have been two approaches to cryopreserving the oocyte: (i) slow freeze-rapid thaw, and (ii) vitrification protocols with rapid cooling-rapid warming. Both methods have incorporated sugars (sucrose) as a beneficial non-permeating extracellular cryoprotectant. Studies of organisms that survive extreme conditions of freezing/dehydration have demonstrated the ability to accumulate intracellular sugars to afford protection and survival. A novel technique using microinjection of sugars into the oocyte for cryopreservation has been developed as an alternative approach to external addition of sugars. Freezing the human oocyte has been a challenging goal; however, developing research and efforts will, in the near future, provide women with an important option for their reproductive health.

Cell Survival↗

Application of rational practice and technical advances for optimizing radiation dose for chest CT.

Though clinical benefits of CT exceed the adverse effects of radiation, the increasing use of CT has raised a compelling case for reducing radiation exposure. This controversy has been compounded by the sheer magnitude of CT examinations being performed annually, alleged overuse, and inappropriate selection of optimum scanning parameters, all of which expose the patient population to increased radiation exposure. Recommended clinical strategies for radiation dose optimization include optimization of scanning parameters and creating awareness and adopting guidelines for legitimate indications for CT scanning to avoid overuse and hence, the associated over-exposure. Whereas technological advances have increased the applications of the modality, it is also assisting in development of promising techniques to reduce associated radiation exposure, while maintaining "optimum image quality" needed to make a confident diagnosis. The present pictorial essay describes the fundamentals of CT radiation exposure and need for CT radiation dose reduction on the basis of documented scanning practices and technological advances.

Humans↗

Radiation from "extra" images acquired with abdominal and/or pelvic CT: effect of automatic tube current modulation.

PURPOSE: To retrospectively determine the number and usefulness of images acquired beyond the intended anatomic area of interest with abdominal and/or pelvic computed tomography (CT) and to assess the effect of automatic tube current modulation (ATCM) on associated radiation. MATERIALS AND METHODS: Superior and inferior levels at routine abdominal and/or pelvic CT were defined as the dome of the diaphragm and the inferior margin of the pubic symphysis, respectively. Records of 106 consecutive examinations (male-to-female ratio, 45:61; age range, 21-86 years) performed from June 1 to June 30, 2003, were reviewed to determine the number of "extra" images. Sixty-two abdominal and/or pelvic CT examinations performed concurrently with chest or thigh CT or for trauma were not included in the 106. Abdominal and/or pelvic CT was performed with either ATCM (n = 44) or manual selection of tube current (n = 62). CT parameters recorded for each extra image included tube current, peak kilovoltage, and gantry rotation time. Mean and median tube current-time products were calculated for extra images. Extra images were analyzed for pathologic findings. Statistical analysis was performed with the Student t test. RESULTS: Extra images were acquired above the dome of the diaphragm in 103 (97%) of 106 examinations and below the pubic symphysis in 100 (94%) of 106. A total of 1,280 extra images were acquired in 106 examinations (mean, 12 images per examination). Nineteen additional findings were observed on extra images. With ATCM, mean tube current-time product was 74.5 and 120.6 mAs for extra images acquired above the diaphragm and below the pubic symphysis, respectively; with manual selection, mean tube current-time products were 167.5 and 168.3 mAs (P <.05). CONCLUSION: Most extra images acquired at abdominal and/or pelvic CT contributed no additional information. With ATCM, the radiation dose was reduced by a mean of 56% (median, 72%) for extra images above the diaphragm and 29% (median, 36%) for images below the pubic symphysis, compared with dose levels with manual selection.

Adult↗

Comparison of Z-axis automatic tube current modulation technique with fixed tube current CT scanning of abdomen and pelvis.

PURPOSE: To compare image quality, diagnostic acceptability, and radiation exposure associated with 16-section multi-detector row computed tomographic (CT) examinations of abdomen and pelvis performed with z-axis modulation technique of automatic tube current modulation and with manual selection of fixed tube current. MATERIALS AND METHODS: Sixty-two consecutive subjects (mean age, 60 years; age range, 19-84 years; male-to-female ratio, 35:27) underwent follow-up CT of abdomen and pelvis with use of a 16-section multi-detector row scanner and z-axis modulation technique (10.5-12.0-HU noise index, 10-380 mA). Scanning parameters included 140 kVp, 0.5-1.0-second gantry rotation time, 0.938:1 beam pitch, and 5-mm reconstructed section thickness. For each subject, images obtained with z-axis modulation were compared with previous images obtained with fixed tube current (200-300 mA) and with other parameters identical. Images were compared for noise and diagnostic acceptability by two subspecialty radiologists using a five-point scale (1, unacceptable; 3, acceptable; 5, excellent) at five levels: upper liver at diaphragm, porta hepatis, right kidney hilum, iliac crest, and upper margin of acetabulum. Tube current and gantry rotation time used for acquisitions at these levels were recorded. Data were analyzed with parametric and nonparametric statistical tests. RESULTS: Although no significant differences were found (P =.34), images acquired with z-axis modulation at the levels of the upper liver (diaphragm) and acetabulum had a higher noise and lower diagnostic quality, compared with images acquired with fixed tube current. Compared with fixed tube current, z-axis modulation resulted in tube current-time product reduction in 54 (87%) of 62 examinations (mean reduction, 71.2 mAs) and increase in eight (13%) (mean increase, 17.0 mAs). CONCLUSION: Compared with manually selected fixed tube current, z-axis automatic tube current modulation resulted in reduced tube current-time product and similar image noise and diagnostic acceptability at CT of abdomen and pelvis.

Abdominal Neoplasms↗

Detection and characterization of lesions on low-radiation-dose abdominal CT images postprocessed with noise reduction filters.

PURPOSE: To assess the effect of noise reduction filters on detection and characterization of lesions on low-radiation-dose abdominal computed tomographic (CT) images. MATERIALS AND METHODS: Low-dose CT images of abdominal lesions in 19 consecutive patients (11 women, eight men; age range, 32-78 years) were obtained at reduced tube currents (120-144 mAs). These baseline low-dose CT images were postprocessed with six noise reduction filters; the resulting postprocessed images were then randomly assorted with baseline images. Three radiologists performed independent evaluation of randomized images for presence, number, margins, attenuation, conspicuity, calcification, and enhancement of lesions, as well as image noise. Side-by-side comparison of baseline images with postprocessed images was performed by using a five-point scale for assessing lesion conspicuity and margins, image noise, beam hardening, and diagnostic acceptability. Quantitative noise and contrast-to-noise ratio were obtained for all liver lesions. Statistical analysis was performed by using the Wilcoxon signed rank test, Student t test, and kappa test of agreement. RESULTS: Significant reduction of noise was observed in images postprocessed with filter F compared with the noise in baseline nonfiltered images (P =.004). Although the number of lesions seen on baseline images and that seen on postprocessed images were identical, lesions were less conspicuous on postprocessed images than on baseline images. A decrease in quantitative image noise and contrast-to-noise ratio for liver lesions was noted with all noise reduction filters. There was good interobserver agreement (kappa = 0.7). CONCLUSION: Although the use of currently available noise reduction filters improves image noise and ameliorates beam-hardening artifacts at low-dose CT, such filters are limited by a compromise in lesion conspicuity and appearance in comparison with lesion conspicuity and appearance on baseline low-dose CT images.

Adult↗

Sixteen-detector row CT of abdomen and pelvis: study for optimization of Z-axis modulation technique performed in 153 patients.

PURPOSE: To retrospectively determine the optimal noise indexes required to obtain diagnostically acceptable computed tomographic (CT) images of the abdomen and pelvis with z-axis modulation. MATERIALS AND METHODS: Ninety-five patients underwent 16-section multi-detector row CT of the abdomen and pelvis with z-axis modulation at noise indexes of 10.5, 11.0, 11.5, and 12.0 HU with 10-380 mA. Subsequently, 58 patients were scanned at noise indexes of 12.5 and 15.0 HU with 75-380 mA. The weights of all subjects were recorded, and transverse and anteroposterior diameters were measured. The CT images were evaluated for abnormalities and graded for image quality in terms of noise and diagnostic acceptability by using a five-point scale. Objective noise in the liver parenchyma was measured, and the tube current was recorded at each section in all 153 patients. Statistical analyses were performed to determine the appropriate noise index and to assess the effect of patient weight and abdominal diameters on image noise and diagnostic acceptability at different noise indexes. Tube current-time products (in milliampere seconds) at various noise indexes were compared with those at CT previously performed without z-axis modulation. RESULTS: No significant difference in subjective image noise or diagnostic acceptability was found at noise indexes of 10.5-15.0 HU (P =.14), and objective noise was significantly inferior only at a noise index of 15.0 HU (P =.009). Compared with CT scanning at a 10.5-HU noise index, CT scanning at 12.5- and 15.0-HU noise indexes yielded, respectively, 10.0% and 41.3% reductions in radiation exposure. Patient weight and abdominal diameters affected subjective image quality. CONCLUSION: Use of a 15.0-HU noise index at 75-380 mA results in acceptable subjective image noise and diagnostic acceptability but significantly greater objective image noise at routine abdominal-pelvic CT. For greater image quality demands, a noise index of 12.5 HU results in acceptable image quality and a 19.6% reduction in radiation exposure.

Abdomen↗

Can noise reduction filters improve low-radiation-dose chest CT images? Pilot study.

Effect of noise reduction filters on chest computed tomographic (CT) images acquired with 50% radiation dose reduction was evaluated. Two sets of images were acquired with multi-detector row CT at standard (220-280 mA) and 50% reduced (110-140 mA) tube current at the level of the carina. After postprocessing with six noise reduction filters, images were compared with baseline standard-dose images for noise, sharpness, and contrast in lungs, mediastinum, and chest wall. Quantitative image noise was measured in descending thoracic aorta. Modulation transfer functions were calculated from CT images of 50-microm wire. Noise reduction filters reduced image noise on low-radiation-dose chest CT images, with some compromise in image sharpness and contrast assessed qualitatively, and slightly altered modulation transfer function at higher spatial frequencies.

Aged↗

Low-dose CT of the abdomen: evaluation of image improvement with use of noise reduction filters pilot study.

A prospective assessment of improvement in image quality at low-radiation-dose computed tomography (CT) of the abdomen by using noise reduction filters was performed. CT images acquired at standard and 50% reduced tube current were processed with six noise reduction filters and evaluated by three radiologists for image noise, sharpness, contrast, and overall image quality in terms of abdominal organ depiction. Quantitative image noise and contrast-to-noise ratio were measured. Baseline low-dose CT images were significantly worse than standard-dose CT images (P <.05). A statistically significant reduction of noise in low-dose images processed with three filters was noted. In conclusion, use of noise reduction filters decreased image noise at low-dose CT.

Aged↗

Quantitative microinjection of trehalose into mouse oocytes and zygotes, and its effect on development.

Sugars such as trehalose are effectively used by various organisms as protective agents to undergo anhydrobiosis and cryobiosis. The objective of this study was first to establish a method for quantitative delivery of trehalose as a model sugar into oocytes, and then to evaluate its effect on development of mouse zygotes. To this end, a quantitative microinjection technique was developed using volumetric response of microdroplets suspended in dimethylpolysilaxene. To verify accuracy of this technique, both microdroplets and oocytes were microinjected with fluorophore-labeled dextran. Thereafter, injection volumes were calculated from fluorescence intensity, and volumetric responses of both microdroplets and oocytes. Comparison of calculated injection volumes revealed that this technique reflects microinjection into oocytes with pL-accuracy. The next series of experiments focused on toxicity of injection buffers (i.e., 10mM Tris and 15mM Hepes) and trehalose. Microinjection of Hepes and Tris buffer in the presence of 0.1M trehalose resulted in blastocyst rates of 86 and 72%, respectively, without a significant difference when compared to controls (86%). In subsequent experiments, Hepes was used as the injection buffer, and embryonic development of zygotes was studied as a function of intracellular trehalose concentrations. Microinjection of trehalose up to 0.15M resulted in development to blastocyst stage similar to controls (85 and 87%, respectively) while the blastocyst rate was significantly decreased (43%) in the presence of 0.20M intracellular trehalose. When transferred to foster mothers, trehalose-injected zygotes (0.1M) implanted and developed to day 16 fetuses similar to controls, healthy pups were born. The findings of this study suggest that trehalose at effective intracellular concentrations does not impair development of mouse zygotes.

Animals↗

Placental villitis of unclear etiology during ovum donor in vitro fertilization pregnancy.

OBJECTIVE: Preliminary observations by a single pathologist at our institution revealed a 75% incidence of villitis of unexplained etiology in ovum donor in vitro fertilization pregnancies. Because the incidence of villitis of unexplained etiology in the general population is approximately 10%, we conducted a controlled study to compare the incidence of villitis of unexplained etiology in ovum donor in vitro fertilization pregnancies to that in in vitro fertilization pregnancies that do not use donated ova. STUDY DESIGN: Placental specimens of ovum donor in vitro fertilization pregnancies were matched randomly with pregnancies that resulted from both fresh and frozen/thawed native oocyte in vitro fertilization from March 5, 1995, to October 10, 2001, and examined in a blinded fashion by a single pathologist (D. J. R.) for villitis of unexplained cause. The incidence of villitis of unexplained etiology was analyzed in 27 patients who underwent ovum donor in vitro fertilization versus 37 patients who underwent native oocyte in vitro fertilization. RESULTS: Villitis of unexplained cause occurred in 22.2% of ovum donor in vitro fertilization pregnancies, 10.8% of native oocyte in vitro fertilization pregnancies (fresh and frozen/thawed combined), and 14.3% of frozen/thawed cycles (P=.21). CONCLUSION: Although the incidence was not statistically different than in in vitro fertilization that used native maternal oocytes, there was a 2-fold increase in villitis of unexplained cause in the ovum donor in vitro fertilization placentas, which suggests that immune-related disorders may be increased in ovum donor pregnancies.

Adult↗

Osmometric behavior of mouse oocytes in the presence of different intracellular sugars.

In order to successfully cryopreserve oocytes using low concentrations of intracellular sugars, it is important to characterize their osmotic response in the presence of these intracellular sugars. In the present study, murine (B6D2F1) oocytes were microinjected with 0.8M glucose, trehalose or stachyose solutions to achieve an intracellular concentration equivalent to 0.1M, and then exposed to hypertonic solutions of increasing strength by supplementing an isotonic solution with 0.2, 0.3, 0.5, and 0.7 M of trehalose. Analysis of volumetric response of microinjected oocytes showed that the oocytes behaved as ideal osmometers in the presence of intracellular sugars and satisfied the Boyle van't Hoff relationship. Extrapolation of the osmotically inactive fraction (V macro b) from the Boyle van't Hoff relationship yielded values of 0.188+/-0.028, 0.212+/-0.042, 0.197+/-0.044, and 0.211+/-0.042 for control, glucose, trehalose and stachyose-injected oocytes, respectively. The present data revealing osmometric behavior of mouse oocytes in the presence of different intracellular sugars are important for the optimization of cryopreservation protocols using sugars.

Animals↗

Beneficial effect of microinjected trehalose on the cryosurvival of human oocytes.

OBJECTIVE: To determine the effectiveness of trehalose as an intracellular cryoprotectant for the cryopreservation of human oocytes. DESIGN: In vitro comparative study. SETTING: Clinical and academic research environment at a medical school teaching hospital. PATIENT(S): Women undergoing in vitro fertilization (IVF). INTERVENTION(S): Discarded human oocytes, obtained from IVF patients, were randomly distributed into three groups: control group (no trehalose), extracellular trehalose group (0.5 M extracellular trehalose), and intracellular trehalose group (0.15 M intra- and 0.5 M extracellular trehalose). Trehalose was introduced into oocytes by microinjection. The oocytes in each group were cooled to different temperatures (i.e., -15 degrees C, -30 degrees C, and -60 degrees C) at rate of 1 degrees C/minute and thawed at ambient air temperature. Survival was examined after overnight culture. MAIN OUTCOME MEASURE(S): Survival of human oocytes cryopreserved in the presence and absence of trehalose. RESULT(S): The majority of oocytes in the intracellular trehalose group survived cooling to -15 degrees C (63%), -30 degrees C (53%), and -60 degrees C (66%). In contrast, only a small number of oocytes in both the control (13%) and extracellular trehalose group (22%) survived cooling to -15 degrees C, while all oocytes degenerated when cooled to -30 degrees C and -60 degrees C. CONCLUSION(S): Small amounts of intracellular trehalose in the absence of any other cryoprotectant provide a significant protection against freeze-associated stresses. Our results suggest that sugars such as trehalose should be considered as intracellular cryoprotectants for cryopreservation of human oocytes.

Cell Survival↗