A cross-sectional analysis of executive function in Down syndrome from 2 to 35 years.

BACKGROUND: Previous research has indicated a unique profile of executive function (EF) in children and adolescents with Down syndrome (DS). However, there is a paucity of research on EF in adults with DS. This study aimed to gain a broader understanding of strengths and weaknesses in EF in DS from 2 to 35 years. METHOD: Parents of 112 individuals with DS between 2 and 35 years participated in this study. Parents either completed the Behaviour Rating Inventory of Executive Function - for individuals 6+ years - or the Behaviour Rating Inventory of Executive Function Preschool Version - for children 2-5 years. RESULTS: Results suggest not only overall difficulties but also patterns of strength and weakness within EF for individuals with DS. For the 2 to 5-year-old group, emotional control and shift were relative strengths, planning/organisation and inhibit were intermediate skills, and working memory was a relative weakness. For the 6 to 18-year-old group, emotional control and organisation of materials were relative strengths, inhibit and initiate were intermediate skills, and working memory, monitor, planning/organisation, and shift were relative weaknesses. Most abilities were consistent from 2 to 18 years, except shift, which decreased in preadolescence before beginning to recover in adolescence. Across the full age range (2-35 years), composite scores indicated quadratic trends in inhibit, working memory, and planning/organisation, and a cubic trend in shift, with EF abilities generally declining in middle childhood before recovering in adulthood. CONCLUSIONS: This study extends previous research on EF in DS by providing an initial description of EF profiles across the lifespan. More longitudinal and behavioural research is needed to further characterise the development of EF in DS.

Post-tooth extraction sepsis without locoregional infection--a population-based study in Taiwan.

OBJECTIVE: To investigate the incidence and risk factors of post-tooth extraction sepsis in patients without locoregional infection. SUBJECTS AND METHODS: We assessed all claim records of the Taiwanese National Health Insurance program in 2005. Admissions for patients aged > or =16 years containing a discharge diagnosis of sepsis, and who received tooth extraction within 14 days before the admission were identified. Patient charts were reviewed to confirm the diagnosis of sepsis and rule out other infection sources. The relationship between postextraction sepsis (PES) and clinical parameters was analyzed. RESULTS: Thirty-three of the 2 223 971 extraction cases met the criteria of PES, an incidence of 1.48 per 100 000, and seven patients (21.2%) died of the disease. Aging significantly increased the risk of PES (P < 0.001). Pre-existing comorbidities were found in 20 of the 33 cases, with diabetes mellitus and hematologic diseases the most common. The method, number, and position of extraction had no influence on PES incidence. Blood cultures were positive in 25 patients (75.8%) and isolates included species of the Streptococcus, Actinomyces, Klebsiella, Bacteroides, Prevotella, and Enterococcus genera. CONCLUSION: Tooth extraction is associated with a low but significant risk of postoperative sepsis, especially in the elderly and patients with underlying diseases.

Cell-mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit.

Betel quid (BQ) chewing is popular in Taiwan, India, and many southeast-Asian countries. BQ chewing has strong association with the risk of oral leukoplakia (OL), oral submucous fibrosis (OSF), and oral cancer (OC). BQ components exhibit genotoxicity and may alter the structure of DNA, proteins and lipids, resulting in production of antigenicity. BQ ingredients are also shown to induce keratinocyte inflammation by stimulating the production of prostaglandins, TNF-alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in keratinocytes. These events may provoke tissue inflammation, early cell-mediated immunity (CMI), and immune surveillance in BQ chewers. However, BQ components also directly affect the functional activities of immunocompotent cells, and moreover tumor cells may hypo-respond to the CMI via diverse mechanisms such as induction of apoptosis of lymphocytes, induction of production of suppressor T cells, downregulation of MHC molecules in tumor cells, etc. Clinically, an alteration in lymphocyte subsets, a decrease in total number of lymphocytes, and a reduction in functional activities of CMI have been observed in isolated peripheral blood mononuclear cells (PBMC) and tumor infiltrated lymphocytes (TIL) in patients with OSF, OL or OC. Adaptation of tumor cells to immune system may promote clonal selection of resistant tumor cells, leading to immune tolerance. Future studies on effects of BQ components on CMI and humoral immunity in vitro and in vivo can be helpful for chemoprevention of BQ-related oral mucosal diseases. To elucidate how virus infection, tobacco, alcohol and BQ consumption, and other environmental exposure affect the immune status of patients with oral premalignant lesions or OC will help us to understand the immunopathogenesis of OC and to develop immunotherapeutic strategies for OC.

Automatic three-dimensional multimodality registration using radionuclide transmission CT attenuation maps: a phantom study.

UNLABELLED: Coregistration of images from a single subject, acquired by different modalities, is important in clinical diagnosis, surgery and therapy planning. The purpose of this study was to evaluate, using a physical torso phantom, a novel, fully automated method for three-dimensional image registration of CT and SPECT, using radionuclide transmission (RNT) attenuation maps. METHODS: We obtained CT scans and SPECT scans paired with RNT maps of an anthropomorphic cardiac phantom. RNT attenuation maps were acquired using an uncollimated 99mTc-filled flood source. RNT and SPECT scans were acquired in the same spatial orientation (usual clinical practice in nonuniform attenuation correction). In addition, CT attenuation maps (CTMAPs) for 99mTc SPECT were generated from CT by linear energy scaling. RNT maps were registered to CT and CTMAPs by iterative simplex minimization of count difference and uniformity index (sum of RNT map intensity variances corresponding to each intensity level in the CT volume). In each iteration, three shifts and three angles were adjusted. To register SPECT to CT, we applied the RNT transformation parameters to SPECT. RESULTS: RNT maps could be registered to CT and CTMAP images using both criteria. The average three-dimensional distance between landmark and automated registration was 2.5 +/- 1.2 mm for count difference and 3.3 +/- 1.3 mm for uniformity index. The three-dimensional reproducibility errors were 1.2 +/- 0.7 mm for count difference, 2.1 +/- 0.5 mm for uniformity index and 2.3 +/- 1.0 mm for manual marker registration. The minimization of uniformity index was robust when up to 50% CT or RNT slices were missing and was not affected significantly (<2 mm) by realistic variation in CT values (+/- 12 Hounsfield units). CONCLUSION: In addition to typical use in nonuniform attenuation correction, RNT maps can be used for fully automated three-dimensional registration of SPECT to CT. Such registration is not affected by features and quality of SPECT images and avoids difficulties associated with fiducial markers. Our method can be applied to SPECT-CT registration of various organs, such as brain, heart, lungs, breasts and abdomen, including oncological scans.

Nonisotropic attenuation in SPECT: phantom tests of quantitative effects and compensation techniques.

A quantitative study of nonisotropic attenuation in SPECT imaging is presented. The study includes a case where the spatial distribution of the attenuation coefficient is nonuniform, as well as a case where the photon path length in the attenuating medium is variable as a function of direction. The effects are studied using phantoms with known source activity and density distributions. Reconstructed images of the phantoms with and without attenuation compensation are compared with the source distribution. Three methods are used to provide partial attenuation compensation, using effective attenuation coefficients. These coefficients include some of the effects of photon scatter, but scatter is not explicitly treated. One attenuation compensation method involves a multiplicative postprocessing correction using an assumed constant attenuation coefficient. A modification of this technique is implemented using the correct nonuniform attenuation map to determine the multiplication factors. A single-iteration technique is used to provide a more complete compensation. The results indicate that nonuniform attenuation can produce significant distortion in line spread functions and in larger distributed sources. This distortion can alter volume determinations, quantitation measurements, and the shape of small objects, and can cause misplacement of counts into regions of low density. The distortion cannot be eliminated by the multiplicative postprocessing correction, but the single-iteration technique can significantly decrease the distortion.

Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: roles of glutathione and reactive oxygen species.

Hydroxychavicol (HC; 10 - 50 microM), a betel leaf component, was found to suppress the 2% H(2)O(2)-induced lucigenin chemiluminescence for 53 - 75%. HC (0.02 - 2 microM) was also able to trap superoxide radicals generated by a xanthine/xanthine oxidase system with 38 - 94% of inhibition. Hydroxyl radicals-induced PUC18 plasmid DNA breaks was prevented by HC (1.6 - 16 microM). A 24-h exposure of KB cells to HC (0.5, 1 mM) resulted in 54 - 74% cell death as analysed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. HC (10, 50 microM) further suppressed the growth of KB cells (15 and 76%, respectively). Long-term colony formation of KB cells was inhibited by 51% with 10 microM HC. Pretreatment of KB cells with 100 microM HC inhibited the attachment of KB cells to type I collagen and fibronectin by 59 and 29%, respectively. Exposure of KB cells to 0.1 mM HC for 24 h resulted in cell cycle arrest at late S and G2/M phase. Increasing the HC concentration to 0.25 and 0.5 mM led to apoptosis as revealed by detection of sub-G(0)/G(1) peaks with a concomitant decrease in the number of cells residing in late S and G(2)/M phase. Inducing the apoptosis of KB cells by HC was accompanied by marked depletion in reduced form of GSH (>0.2 mM) and the increasing of reactive oxygen species production (>0.1 mM) as analysed by CMF- and DCF-single cell fluorescence flow cytometry. These results indicate that HC exerts antioxidant property at low concentration. HC also inhibits the growth, adhesion and cell cycle progression of KB cells, whereas its induction of KB cell apoptosis (HC>0.1 mM) was accompanied by cellular redox changes.

Collagen biosynthesis in human oral submucous fibrosis fibroblast cultures.

To investigate the mechanism of collagen accumulation in oral submucous fibrosis (OSF) tissues, we examined the biosynthesis of collagen in fibroblast cultures established from OSF lesions. Fibroblasts obtained from four of ten OSF specimens showed more than a 1.5-fold increase in the production of collagens compared with fibroblasts from age-, sex-, and passage-matched normal controls (p < 0.05). When the relative amounts of collagen synthesis were estimated by SDS polyacrylamide gel electrophoresis, it was found that both OSF and control cells produced about 85% type I collagen and 15% type III collagen. The ratio of alpha 1(I) to alpha 2(I) chains was about 3:1 in OSF cells instead of the 2:1 expected for type I collagen. The excess alpha 1(I) chains could mean that collagen type I trimer was synthesized by the fibroblasts. These findings suggest that collagen overproduction and a reduced degradation of the structure-stable collagen type I trimer synthesized by OSF fibroblasts might contribute to the accumulation of collagen in OSF lesions in vivo. The mechanism(s) of increased procollagen production were analyzed by Northern blot, slot blot, and Southern blot. The OSF fibroblast strains with elevated collagen production also contained higher-than-normal levels of procollagen mRNA, and the ratios of alpha 1(I), alpha 2(I), and alpha 1(III) procollagen mRNAs were compatible with the results of corresponding procollagen alpha chains. The gene copy number of pro alpha 2(I) collagen gene in OSF fibroblasts was about 1.05. No gene amplification was found. These results indicate that expression of these procollagen genes in cultured fibroblasts is regulated at the transcriptional level.

Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro.

To understand the role of betel quid (BQ) in the pathogenesis of oral submucous fibrosis (OSF) and oral cancer, we used DNA damage, cytotoxicity, and cell proliferation assays to study the pathobiological effects of aqueous extracts of three BQ constituents [betel nut (Areca catechu, BN), inflorescence of Piper betle (IPB), and lime], one BN alkaloid (arecoline), and one BN polyphenol [(+)-catechin] on cultured oral mucosal fibroblasts. Extracts of BN and IPB induced DNA strand break formation in a dose-dependent manner. Extracts of BN and IPB, (+)-catechin, and arecoline decreased cell survival and proliferation in a dose-dependent manner. However, aqueous extract of lime (50-800 micrograms/mL) increased cell proliferation by 20-40%. These results indicate that BQ contains not only genotoxic and cytotoxic agents, but also compounds which stimulate cell proliferation. These compounds may act synergistically in the pathogenesis of OSF and oral cancer in BQ chewers. In addition, five anti-oxidants [glutathione (GSH), cysteine, mannitol, catalase, and superoxide dismutase (SOD)] were tested for their protective effects against the cytotoxicity of BQ constituents. GSH (1.95 and 2.6 mmol/L) and cysteine (4 and 8 mmol/L) prevented the arecoline-induced cytotoxicity. In contrast, mannitol, catalase, and SOD did not decrease the arecoline-induced cytotoxicity. These results indicate that thiol depletion, but not the attack of oxygen free radicals, could be the mechanism for arecoline cytotoxicity. GSH could also protect cells from the cytotoxicity of IPB extract. Increasing dietary intake of GSH-rich foods or dietary supplements of GSH may have chemopreventive potential to reduce BQ-associated oral lesions.

Eugenol triggers different pathobiological effects on human oral mucosal fibroblasts.

Pathobiological effects of eugenol (4-allyl-2-methoxyphenol), a major constituent of betel quid (BQ), were studied on oral mucosal fibroblasts. At a concentration higher than 3 mmol/L, eugenol was cytotoxic to oral mucosal fibroblasts in a concentration- and time-dependent manner. Cell death was associated with intracellular depletion of glutathione (GSH). Most of the GSH was depleted prior to the onset of cell death. At concentrations of 3 mmol/L and 4 mmol/L, eugenol depleted about 45% and 77% of GSH after one-hour incubation. In addition, eugenol decreased cellular ATP level in a concentration- and time-dependent manner. Eugenol also inhibited lipid peroxidation. Inhibition of lipid peroxidation was partially explained by its dose-dependent inhibition of xanthine oxidase activity. The IC50 of eugenol on xanthine oxidase activity was about 0.3 mmol/L. No DNA strand break activity for eugenol was found at concentrations between 0.5 and 3 mmol/L. Taken together, frequent exposure of oral mucosa to a high concentration of eugenol during the chewing of BQ might be involved in the pathogenesis of oral submucous fibrosis and oral cancer via its cytotoxicity. In contrast, eugenol at a concentration less than 1 mmol/L might protect cells from the genetic attack of reactive oxygen species via inhibition of xanthine oxidase activity and lipid peroxidation.

Association between genetic polymorphism of tumor necrosis factor-alpha and risk of oral submucous fibrosis, a pre-cancerous condition of oral cancer.

Many cytokines have been thought to play important roles in the pathogenesis of oral submucous fibrosis (OSF), an areca nut chewing-specific pre-cancerous condition characterized by the deposition of collagen in oral submucosa. Tumor necrosis factor-alpha (TNF-alpha), situated in the class III region of human leukocyte antigen (HLA), is a mediator with multiple functions, including the regulation of inflammatory reaction and transcriptions of collagen and collagenase. In total, 809 male subjects were recruited for assessment of the association of OSF with a bi-allelic promoter-region (-308) polymorphism on the TNFA gene. The high production allele, TNF2, was significantly lower among OSF subjects (n = 166) than in areca-chewing controls (n = 284). This association was independent of oral cancer status. The multivariate-adjusted odds ratio for the TNFA 11 genotype was 2.6 (95% confidence interval = 1.4-4.9; p = 0.004). The finding may imply a multifunctional etiological factor of TNF-alpha in OSF pathogenesis.

Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives.

Betel quid (BQ)-chewing is a popular oral habit with potential links to the occurrence of oral cancer. Many of the literature-based studies reveal that areca nut (AN) extract may demonstrate mutagenic and genotoxic effects, in addition to inducing preneoplastic as well as neoplastic lesions in experimental animals. Areca nut should, thus, be highly suspected as a human carcinogen. Toxicity studies relating to AN-contained polyphenols and tannins are not conclusive, with both carcinogenic and anti-carcinogenic effects being reported. The mutagenicity and genotoxicity of areca alkaloids has been detected by many short-term assays. However, their genotoxicity to oral fibroblasts and keratinocytes, the target cells of BQ, has not been identified. It would thus appear that AN toxicity is not completely due to its polyphenol, tannin and alkaloid content. The single agent which is responsible for AN carcinogenicity awaits further clarification. Reactive oxygen species produced during auto-oxidation of AN polyphenols in the BQ-chewer's saliva, are crucial in the initiation and promotion of oral cancer. Nitrosation of areca alkaloids also produces AN-specific nitrosamines, that have been demonstrated to be mutagenic, genotoxic and are capable of inducing tumors in experimental animals. Arecaidine and AN extract are further suggested to be tumor promoters. Antioxidants such as glutathione and N-acetyl-L-cysteine can potentially prevent such AN-elicited cytotoxicity. Further studies are needed to delineate the metabolism of AN ingredient and their roles in the multi-step chemical carcinogenesis, in order to enhance the success of the future chemoprevention of oral cancer and oral submucous fibrosis.

Expression of proliferating cell nuclear antigen (PCNA) in oral submucous fibrosis, oral epithelial hyperkeratosis and oral epithelial dysplasia in Taiwan.

To test whether the oral epithelia of oral submucous fibrosis (OSF), epithelial hyperkeratosis (EH) and epithelial dysplasia (ED) may have increased proliferative activity under the long-term exposure to areca quid ingredients and whether there is an increased expression of proliferating cell nuclear antigen (PCNA) in oral premalignant lesions with disease progression, we used an immunohistochemical technique with the mouse monoclonal antibody PC10 to investigate PCNA expression in histologic sections of OSF, EH, ED and normal oral mucosa (NOM). Positive PCNA staining was found mainly in basal and parabasal epithelial cells in all specimens of OSF, EH, ED and NOM. The mean PCNA labeling indices (LI) in NOM, OSF, EH and ED were 8.8+/-2.7%, 22.1+/-12.5%, 25.5+/-5. 2% and 44.9+/-15.4%, respectively. Significant differences in the PCNA LI were noted between NOM and OSF (P<0.01), EH (P<0.001) or ED (P<0.001), as well as between ED and OSF (P<0.001) or EH (P<0.01). The gradual increase of PCNA expression with the morphologic transformation of normal epithelial cells into dysplastic epithelial cells suggests that there is increased proliferative activity in oral premalignant lesions with disease progression. However, no significant correlation was found between PCNA LI in OSF epithelium and the clinicohistologic parameters of OSF. In addition, the mean PCNA LI of p53-positive OSF cases (23.7+/-12.0%) was very close to that of p53-negative OSF cases (23.9+/-13.1%), suggesting that there was no association between PCNA and p53 expression in OSF.

Prevention of the areca nut extract-induced unscheduled DNA synthesis of gingival keratinocytes by vitamin C and thiol compounds.

There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is the major risk factor of oral cancer in India, Taiwan, South Africa and numerous other countries. Areca nut (AN) extract, the main component of BQ, exerts cytotoxicity and genotoxicity to several types of cells. In the present study, AN extract induced the unscheduled DNA synthesis (UDS) of gingival keratinocytes (GK). Vitamin C, at concentration of 50 and 200 microg/ml prevented the AN-induced UDS by 41 and 56%, respectively. Glutathione (GSH, 1-3 mM) and N-acetyl-L-cysteine (NAC, 1-3 mM) also protected the AN-induced UDS by 89-100 and 76-90%. These preventive effects were not due to cytotoxicity as analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Deferoxamine (20 and 30 mM), an iron chelator and a free radical scavenger, also prevented AN extract induced UDS of GK by 30-55%. On the contrary, banthocuproine (50-200 microM, a copper chelator) and 1,10-phenanthroline (50, 100 microM, a lipid permeable iron chelator), lacked preventive effects. Specific reactive oxygen species scavengers such as dimethyl-sulfoxide (2%), mannitol (10-20 mM), dimethylthiourea (10-20 mM), pyruvate (10 mM), catalase (200 and 400 U/ml), and superoxide dismutase (50 and 200 U/ml) also lacked these preventive effects. Moreover, higher concentrations of H(2)O(2) (0.5-1 mM) inhibited the basal levels of UDS by 19-37%. Interestingly, NAC, GSH, Vitamin C and deferoxamine cannot prevent the AN-induced morphological changes of GK at similar concentrations. These results reveal that AN extract-induced UDS of GK is associated with free radical reactions. Possibly different ingredients of AN is responsible for genotoxicity and cytotoxicity. Vitamin C, GSH and NAC may be potentially used in the future for chemoprevention of BQ chewing related oral mucosal lesions.

Preconstruction restoration of myocardial single photon emission computed tomography images.

A restoration scheme for single photon emission computed tomography (SPECT) images that performs restoration before reconstruction (preconstruction restoration) from planar (projection) images is presented. A comparison is performed between results obtained in this study and those obtained by a method reported previously where the restoration is performed after reconstruction (postreconstruction restoration). The filters investigated are the Wiener and power spectrum equalization filters. These filters are applied to SPECT images of a hollow cylinder phantom and a cardiac phantom acquired on a Siemens Rota camera. Quantitative analyses of the results are performed through measurements of contrast ratios and root mean squared errors. The preconstruction restored images show a significant decrease in the root mean squared error and an increase in contrast over the postconstruction restored images.

Restoration of gamma camera-based nuclear medicine images.

Experiments were conducted using a Siemens Rota camera to study the applicability of two linear shift-invariant (LSI) filters, namely, the Wiener and power spectrum equalization filters, for restoration of planar projections and single-photon-emission computed tomography (SPECT) images. In the restoration scheme, the system transfer function, computed from a line source image, is modeled by a 2-D Gaussian function. The noise power spectrum is modeled as a constant for planar images and as a ramp for SPECT images. The filters have been applied to restore computer-simulated 1-D and 2-D projections and SPECT images of two simple phantoms, 2-D projections of two phantoms obtained from the Siemens Rota camera, and SPECT images of a cardiac phantom obtained from the Siemens Rota camera. The filters are shown to perform partial restoration. Considerable noise suppression and detail enhancement have been observed in the restored images. quantitative measurements such as root-mean-squared error and contrast ratio have been used for objective analysis of the results, which are encouraging.

Two-dimensional restoration of single photon emission computed tomography images using the Kalman filter.

The discrete filtered backprojection (DFBP) algorithm used for the reconstruction of single photon emission computed tomography (SPECT) images affects image quality because of the operations of filtering and discretization. The discretization of the filtered backprojection process can cause the modulation transfer function (MTF) of the SPECT imaging system to be anisotropic and nonstationary, especially near the edges of the camera's field of view. The use of shift-invariant restoration techniques fails to restore large images because these techniques do not account for such variations in the MTF. This study presents the application of a two-dimensional (2D) shift-variant Kalman filter for post-reconstruction restoration of SPECT slices. This filter was applied to SPECT images of a hollow cylinder phantom; a resolution phantom; and a large, truncated cone phantom containing two types of cold spots, a sphere, and a triangular prism. The images were acquired on an ADAC GENESYS camera. A comparison was performed between results obtained by the Kalman filter and those obtained by shift-invariant filters. Quantitative analysis of the restored images performed through measurement of root mean squared errors shows a considerable reduction in error of Kalman-filtered images over images restored using shift-invariant methods.

A quantitative comparison of attenuation-weighted backprojection with multiplicative and iterative postprocessing attenuation compensation in SPECT.

Comparisons are made between different analytic attenuation compensation methods used in SPECT imaging. The methods include a multiplicative technique and a single-iterative technique, both applied after filtered backprojection, and two different implementations of an attenuation-weighted filtered backprojection technique (A-W FBP). The methods are compared using simple phantoms of line sources and water-filled circular and elliptical cylinders. both simulated data (without scatter) and experimental data (with scatter) are reconstructed. None of the methods is truly quantitative, even without the presence of scatter, but are potentially useful and improve quantitation. All techniques provide good peak compensation for line sources in attenuating media. The weighted backprojection methods eliminate nearly all deformation due to nonisotropic attenuation for a line source centered in an ellipse. However, the measured noise is amplified by A-W FBP, unless the method is further modified to reduce the amplification.

Noise characteristics for cone beam collimators: a comparison with parallel hole collimator.

In order to evaluate the properties of a cone beam (CB) collimator and three-dimensional filtered backprojection algorithm, the noise characteristics of this collimator configuration were determined and comparisons with a parallel hole (PH) collimator were made. Noise characteristics were evaluated using two approaches: the first consisted of assessing the magnitude of local random fluctuations in the reconstructed images, and the second consisted of assessing the noise texture in these images in the frequency domain by evaluating the noise power spectrum. Data used for these measurements were simulated using Monte Carlo models of SPECT systems equipped with cone beam and parallel hole collimators. Finally, to compare experimentally a specially designed high resolution CB collimator with a high resolution (HRES) PH collimator, measurements of a physical phantom were performed. Results of our studies show better noise magnitude for CB collimators; however, for CB collimators with short focal lengths (40-60 cm) the shape of %RMS noise distributions differs from slice to slice.

X-ray CT monitoring of iceball growth and thermal distribution during cryosurgery.

X-ray CT is able to image the internal architecture of frozen tissue. Phantoms of distilled water, a saline-gelatin mixture, lard and a calf liver-gelatin suspension cooled by a plastic tube acting as a long liquid nitrogen cryoprobe were used to study the relationship between Hounsfield unit (HU) values and temperature. There is a signature change in HU value from unfrozen to completely frozen tissue. No discernible relation exists between temperature in a completely frozen tissue and its HU value for the temperature range achieved with commercial cryoprobes. However, such a relation does exist in the typically narrow region of phase change and it is this change in HU value that is the parameter of concern for quantitative monitoring of the freezing process. Calibration of temperature against change in HU value allows a limited set of isotherms to be generated in the phase change region for direct monitoring of iceball growth. The phase change temperature range, mid-phase change temperature and the absolute value of HU change from completely frozen to unfrozen tissue are shown to be sensitive to the medium. Modelling of the temperature distribution within the region of completely frozen phantom using the infinite cylinder solution to the Fourier heat equation allows the temperature history of the phantom to be predicted. A set of isotherms, generated using a combination of thermal modelling and calibrated HU values demonstrates the feasibility of routine x-ray CT assisted cryotherapy. Isotherm overlay will be a major aid to the cryosurgeon who adopts a fixed target temperature as the temperature below which there is a certainty of ablation of the diseased tissue.

A model for the time-dependent thermal distribution within an iceball surrounding a cryoprobe.

The optimal cooling parameters to maximize cell necrosis in different types of tissue have yet to be determined. However, a critical isotherm is commonly adopted by cryosurgeons as a boundary of lethality for tissue. Locating this isotherm within an iceball is problematic due to the limitations of MRI, ultrasound and CT imaging modalities. This paper describes a time-dependent two-dimensional axisymmetric model of iceball formation about a single cryoprobe and extensively compares it with experimental data. Thermal histories for several points around a CRYOprobe are predicted to high accuracy (5 degrees C maximum discrepancy). A realistic three-dimensional probe geometry is specified and cryoprobe temperature may be arbitrarily set as a function of time in the model. Three-dimensional temperature distributions within the iceball, predicted by the model at different times, are presented. Isotherm locations, as calculated with the infinite cylinder approximation, are compared with those of the model in the most appropriate region of the iceball. Infinite cylinder approximations are shown to be inaccurate when applied to this commercial probe. Adopting the infinite cylinder approximation to locate the critical isotherm is shown to lead the user to an overestimate of the volume of target tissue enclosed by this isotherm which may lead to incomplete tumour ablation.