Computerized Interactive Orthodontic Treatment Planning

Submitted in partial fulfillment of the requirements for a Certificate in Orthodontics, Dept. of Orthodontics, University of Connecticut Health Center, 1975.

Assessment of cone beam computed tomography techniques for imaging lung damage in mice in vivo

Lung damage is a common side effect of chemotherapeutic drugs such as bleomycin. This study used a bleomycin mouse model which simulates the lung damage observed in humans. Noninvasive, in vivo cone-beam computed tomography (CBCT) was used to visualize and quantify fibrotic and inflammatory damage over the entire lung volume of mice. Bleomycin was used to induce pulmonary damage in vivo and the results from two CBCT systems, a micro-CT and flat panel CT (fpCT), were compared to histologic measurements, the standard method of murine lung damage quantification. Twenty C57BL/6 mice were given either 3 U/kg of bleomycin or saline intratracheally. The mice were scanned at baseline, before the administration of bleomycin, and then 10, 14, and 21 days afterward. At each time point, a subset of mice was sacrificed for histologic analysis. The resulting CT images were used to assess lung volume. Percent lung damage (PLD) was calculated for each mouse on both the fpCT (PLDfpcT) and the micro-CT (PLDμCT). Histologic PLD (PLDH) was calculated for each histologic section at each time point (day 10, n = 4; day 14, n = 4; day 21, n = 5; control group, n = 5). A linear regression was applied to the PLDfpCT vs. PLDH, PLDμCT vs. PLDH and PLDfpCT vs. PLDμCT distributions. This study did not demonstrate strong correlations between PLDCT and PLDH. The coefficient of determination, R, was 0.68 for PLDμCT vs. PLDH and 0.75 for the PLD fpCT vs. PLDH. The experimental issues identified from this study were: (1) inconsistent inflation of the lungs from scan to scan, (2) variable distribution of damage (one histologic section not representative of overall lung damage), (3) control mice not scanned with each group of bleomycin mice, (4) two CT systems caused long anesthesia time for the mice, and (5) respiratory gating did not hold the volume of lung constant throughout the scan. Addressing these issues might allow for further improvement of the correlation between PLDCT and PLDH. ^

Prospective gated 64 slice computed tomography in assessment of coronary artery disease: A single center experience and relationship of body mass index to outcomes

Coronary artery disease (CAD) is the most common cause of morbidity and mortality in the United States. While Coronary Angiography (CA) is the gold standard test to investigate coronary artery disease, Prospective gated-64 Slice Computed Tomography (Prosp-64CT) is a new non-invasive technology that uses the 64Slice computed tomography (64CT) with electrocardiographic gating to investigate coronary artery disease. The aim of the current study was to investigate the role of Body Mass Index (BMI) as a factor affecting occurrence of CA after a Prosp-64CT, as well as the quality of the Prosp-64CT. Demographic and clinical characteristics of the study population were described. A secondary analysis of data on patients who underwent a Prosp-64CT for evaluation of coronary artery disease was performed. Seventy seven patients who underwent Prosp-64CT for evaluation for coronary artery disease were included. Fifteen patients were excluded because they had missing data regarding BMI, quality of the Prosp-64CT or CA. Thus, a total of 62 patients were included in the final analysis. The mean age was 56.2 years. The mean BMI was 31.3 kg/m 2. Eight (13%) patients underwent a CA within one month of Prosp-64CT. Eight (13%) patients had a poor quality Prosp-64CT. There was significant association of higher BMI as a factor for occurrence of CA post Prosp-64CT (P<0.05). There was a trend, but no statistical significance was observed for the association of being obese and occurrence of CA (P=0.06). BMI, as well as obesity, were not found to be significantly associated with poor quality of Prosp-64CT (P=0.19 and P=0.76, respectively). In conclusion, BMI was significantly associated with occurrence of CA within one month of Prosp-64CT. Thus, in patients with a higher BMI, diagnostic investigation with both tests could be avoided; rather, only a CA could be performed. However, the relationship of BMI to quality of Prosp-64CT needs to be further investigated since the sample size of the current study was small.^

Trends in utilization of computer tomography (CT) scans for victims of motor vehicle collision (MVCs) in a level I trauma center from 1996 to 2006

Purpose. To evaluate trends in the utilization of head, abdominal, thoracic and other body regions CTs in the management of victims of MVC at a level I trauma center from 1996 to 2006.^ Method. From the trauma registry, I identified patients involved in MVC's in a level I trauma center and categorized them into three age groups of 13-18, 19-55 and ≥56. I used International Classification of Disease (ICD-9-CM) codes to find the type and number of CTs examinations performed for each patient. I plotted the mean number of CTs per patient against year of admission to find the crude estimate of change in utilization pattern for each type of CT. I used logistic regression to assess whether repetitive CTs (≥ 2) for head, abdomen, thorax and other body regions were associated with age group and year of admission for MVC patients. I adjusted the estimates for gender, ethnicity, insurance status, mechanism and severity of injury, intensive care unit admission status, patient disposition (dead or alive) and year of admission.^ Results. Utilization of head, abdominal, thoracic and other body regions CTs significantly increased over 11-year period. Utilization of head CT was greatest in the 13-18 age group, and increased from 0.58 CT/patient in 1996 to 1.37 CT/patient in 2006. Abdominal CTs were more common in the ≥56+ age group, and increased from 0.33 CT/patient in 1996 to 0.72 CT/patient in 2006. Utilization of thoracic CTs was higher in the 56+ age group, and increased from 0.01 CT/patient in 1996 to 0.42 CT/patient in 2006. Utilization of other CTs did not change materially during the study period for adolescents, adults or older adults. In the multivariable analysis, after adjustment for potential confounders, repetitive head CTs significantly increased in the 13-18 age group (95% CI: 1.29-1.87, p=<0.001) relative to the 19-55 age group. Repetitive thoracic CT use was lower in adolescents (95% CI: 0.22-0.70, p=<0.001) relative to the 19-55 age group.^ Conclusion. There has been a substantial increase in the utilization of head, abdominal, thoracic and other CTs in the management of MVC patients. Future studies need to identify if increased utilization of CTs have resulted in better health outcome for these patients. ^

A computerized statistical framework for coalescent analysis

Coalescent theory represents the most significant progress in theoretical population genetics in the past three decades. The coalescent theory states that all genes or alleles in a given population are ultimately inherited from a single ancestor shared by all members of the population, known as the most recent common ancestor. It is now widely recognized as a cornerstone for rigorous statistical analyses of molecular data from population [1]. The scientists have developed a large number of coalescent models and methods[2,3,4,5,6], which are not only applied in coalescent analysis and process, but also in today’s population genetics and genome studies, even public health. The thesis aims at completing a statistical framework based on computers for coalescent analysis. This framework provides a large number of coalescent models and statistic methods to assist students and researchers in coalescent analysis, whose results are presented in various formats as texts, graphics and printed pages. In particular, it also supports to create new coalescent models and statistical methods. ^

An evaluation of sleep hypnotic and stimulant effect on human performance using a computerized psychological test battery

This study evaluated the administration-time-dependent effects of a stimulant (Dexedrine 5-mg), a sleep-inducer (Halcion 0.25-mg) and placebo (control) on human performance. The investigation was conducted on 12 diurnally active (0700-2300) male adults (23-38 yrs) using a double-blind, randomized sixway-crossover three-treatment, two-timepoint (0830 vs 2030) design. Performance tests were conducted hourly during sleepless 13-hour studies using a computer generated, controlled and scored multi-task cognitive performance assessment battery (PAB) developed at the Walter Reed Army Institute of Research. Specific tests were Simple and Choice Reaction Time, Serial Addition/Subtraction, Spatial Orientation, Logical Reasoning, Time Estimation, Response Timing and the Stanford Sleepiness Scale. The major index of performance was "Throughput", a combined measure of speed and accuracy.^ For the Placebo condition, Single and Group Cosinor Analysis documented circadian rhythms in cognitive performance for the majority of tests, both for individuals and for the group. Performance was best around 1830-2030 and most variable around 0530-0700 when sleepiness was greatest (0300).^ Morning Dexedrine dosing marginally enhanced performance an average of 3% with reference to the corresponding in time control level. Dexedrine AM also increased alertness by 10% over the AM control. Dexedrine PM failed to improve performance with reference to the corresponding PM control baseline. With regard to AM and PM Dexedrine administrations, AM performance was 6% better with subjects 25% more alert.^ Morning Halcion administration caused a 7% performance decrement and 16% increase in sleepiness and a 13% decrement and 10% increase in sleepiness when administered in the evening compared to corresponding in time control data. Performance was 9% worse and sleepiness 24% greater after evening versus morning Halcion administration.^ These results suggest that for evening Halcion dosing, the overnight sleep deprivation occurring in coincidence with the nadir in performance due to circadian rhythmicity together with the CNS depressant effects combine to produce performance degradation. For Dexedrine, morning administration resulted in only marginal performance enhancement; Dexedrine in the evening was less effective, suggesting the 5-mg dose level may be too low to counteract the partial sleep deprivation and nocturnal nadir in performance. ^

The use of the computerized and revised vital record in conducting etiologic studies on neural tube defects

The purpose of this study was to evaluate the adequacy of computerized vital records in Texas for conducting etiologic studies on neural tube defects (NTDs), using the revised and expanded National Centers for Health Statistics vital record forms introduced in Texas in 1989.^ Cases of NTDs (anencephaly and spina bifida) among Harris County (Houston) residents were identified from the computerized birth and death records for 1989-1991. The validity of the system was then measured against cases ascertained independently through medical records and death certificates. The computerized system performed poorly in its identification of NTDs, particularly for anencephaly, where the false positive rate was 80% with little or no improvement over the 3-year period. For both NTDs the sensitivity and predictive value positive of the tapes were somewhat higher for Hispanic than non-Hispanic mothers.^ Case control studies were conducted utilizing the tape set and the independently verified data set, using controls selected from the live birth tapes. Findings varied widely between the data sets. For example, the anencephaly odds ratio for Hispanic mothers (vs. non-Hispanic) was 1.91 (CI = 1.38-2.65) for the tape file, but 3.18 (CI = 1.81-5.58) for verified records. The odds ratio for diabetes was elevated for the tape set (OR = 3.33, CI = 1.67-6.66) but not for verified cases (OR = 1.09, CI = 0.24-4.96), among whom few mothers were diabetic. It was concluded that computerized tapes should not be solely relied on for NTD studies.^ Using the verified cases, Hispanic mother was associated with spina bifida, and Hispanic mother, teen mother, and previous pregnancy terminations were associated with anencephaly. Mother's birthplace, education, parity, and diabetes were not significant for either NTD.^ Stratified analyses revealed several notable examples of statistical interaction. For anencephaly, strong interaction was observed between Hispanic origin and trimester of first prenatal care.^ The prevalence was 3.8 per 10,000 live births for anencephaly and 2.0 for spina bifida (5.8 per 10,000 births for the combined categories). ^

Errors in the administration of medication in inpatient hospitals: A systematic review of the research literature on commercial computerized physician order entry systems

Errors in the administration of medication represent a significant loss of medical resources and pose life altering or life threatening risks to patients. This paper considered the question, what impact do Computerized Physician Order Entry (CPOE) systems have on medication errors in the hospital inpatient environment? Previous reviews have examined evidence of the impact of CPOE on medication errors, but have come to ambiguous conclusions as to the impact of CPOE and decision support systems (DSS). Forty-three papers were identified. Thirty-one demonstrated a significant reduction in prescribing error rates for all or some drug types; decreases in minor errors were most often reported. Several studies reported increases in the rate of duplicate orders and failures to remove contraindicated drugs, often attributed to inappropriate design or to an inability to operate the system properly. The evidence on the effectiveness of CPOE to reduce errors in medication administration is compelling though it is limited by modest study sample sizes and designs. ^

A Step in the Right Direction: Development of the Computerized Assessment for Preschool Social Emotional Learning (CAPSEL)

Invited commentary on "Computerizing Social-Emotional Assessment for School Readiness".

Design and Optimization of Four-dimensional Cone-beam Computed Tomography in Image-guided Radiation Therapy

The influence of respiratory motion on patient anatomy poses a challenge to accurate radiation therapy, especially in lung cancer treatment. Modern radiation therapy planning uses models of tumor respiratory motion to account for target motion in targeting. The tumor motion model can be verified on a per-treatment session basis with four-dimensional cone-beam computed tomography (4D-CBCT), which acquires an image set of the dynamic target throughout the respiratory cycle during the therapy session. 4D-CBCT is undersampled if the scan time is too short. However, short scan time is desirable in clinical practice to reduce patient setup time. This dissertation presents the design and optimization of 4D-CBCT to reduce the impact of undersampling artifacts with short scan times. This work measures the impact of undersampling artifacts on the accuracy of target motion measurement under different sampling conditions and for various object sizes and motions. The results provide a minimum scan time such that the target tracking error is less than a specified tolerance. This work also presents new image reconstruction algorithms for reducing undersampling artifacts in undersampled datasets by taking advantage of the assumption that the relevant motion of interest is contained within a volume-of-interest (VOI). It is shown that the VOI-based reconstruction provides more accurate image intensity than standard reconstruction. The VOI-based reconstruction produced 43% fewer least-squares error inside the VOI and 84% fewer error throughout the image in a study designed to simulate target motion. The VOI-based reconstruction approach can reduce acquisition time and improve image quality in 4D-CBCT.

Animations of micro-computed tomography of a pleistocene terebratulid brachiopod

The dorsal valve of a Pleistocene terebratulid brachiopod, Terebratula scillae Seguenza, 1871, has developed a malignant cyst due to colonization in vivo by an endolithic sponge.This trace fossil is a compound boring and bioclaustration structure, representing a boring that has grown in unison with the growth of the cyst. The brachiopod has grown to adult size and growthlines indicate that it was colonised by the sponge when about half grown. Malformation of the shell may not have caused the death of the brachiopod and the sponge does not appear to have outlived its host; both symbionts seem to have died more or less simultaneously. This minus-minus relationship of two symbionts is considered to be a case of 'accidental symbiosis'.

Animation of micro-computed tomography of bioerosion trace Entobia megastoma made by East Australian bioeroding sponge Cliona celata

Endolithic bioerosion is difficult to analyse and to describe, and it usually requires damaging of the sample material. Sponge erosion (Entobia) may be one of the most difficult to evaluate as it is simultaneously macroscopically inhomogeneous and microstructurally intricate. We studied the bioerosion traces of the two Australian sponges Cliona celata Grant, 1826 (sensu Schönberg 2000) and Cliona orientalis Thiele, 1900 with a newly available radiographic technology: high resolution X-ray micro-computed tomography (MCT). MCT allows non-destructive visualisation of live and dead structures in three dimensions and was compared to traditional microscopic methods. MCT and microscopy showed that C. celata bioerosion was more intense in the centre and branched out in the periphery. In contrast, C. orientalis produced a dense, even trace meshwork and caused an overall more intense erosion pattern than C. celata. Extended pioneering filaments were not usually found at the margins of the studied sponge erosion, but branches ended abruptly or tapered to points. Results obtained with MCT were similar in quality to observations from transparent optical spar under the dissecting microscope. Microstructures could not be resolved as well as with e.g. scanning electron microscopy (SEM). Even though sponge scars and sponge chips were easily recognisable on maximum magnification MCT images, they lacked the detail that is available from SEM. Other drawbacks of MCT involve high costs and presently limited access. Even though MCT cannot presently replace traditional techniques such as corrosion casts viewed by SEM, we obtained valuable information. Especially for the possibility to measure endolithic pore volumes, we regard MCT as a very promising tool that will continue to be optimised. A combination of different methods will produce the best results in the study of Entobia.

Mineralogical and stable isotope analyses of carbonates from the eastern Black Sea

Authigenic carbonates associated with cold seeps provide valuable archives of changes in the long-term seepage activity. To investigate the role of shallow-buried hydrates on the seepage strength and fluid composition we analysed methane-derived carbonate precipitates from a high-flux hydrocarbon seepage area ("Batumi seep area") located on the south-eastern Black Sea slope in ca. 850 m. In a novel approach, we combined computerized X-ray tomography (CT) with mineralogical and isotope geochemical methods to get additional insights into the three-dimensional internal structure of the carbonate build-ups. X-ray diffractometry revealed the presence of two different authigenic carbonate phases, i.e. pure aragonitic rims associated with vital microbial mats and high-Mg calcite cementing the hemipelagic sediment. As indicated by the CT images, the initial sediment has been strongly deformed, first plastic then brittle, leading to brecciation of the progressively cemented sediment. The aragonitic rims on the other hand, represent a presumably recent carbonate growth phase since they cover the already deformed sediment. The stable oxygen isotope signature indicates that the high-Mg calcite cement incorporated pore water mixed with substantial hydrate water amounts. This points at a dominant role of high gas/fluid flux from decomposing gas hydrates leading to the deformation and cementation of the overlying sediment. In contrast, the aragonitic rims do not show an influence of 18O-enriched hydrate water. The differences in d18O between the presumably recent aragonite precipitates and the older high-Mg cements suggest that periods of hydrate dissociation and vigorous fluid discharge alternated with times of hydrate stability and moderate fluid flow. These results indicate that shallow-buried gas hydrates are prone to episodic decomposition with associated vigorous fluid flow. This might have a profound impact on the seafloor morphology resulting e.g. in the formation of carbonate pavements and pockmark-like structures but might also affect the local carbon cycle.