Biomedical subjects

Aaron Fenster

Publications and source records attributed to Aaron Fenster.

At least 19 recordsLinked to original sources

PubMed2006

Carotid ultrasound phenotypes in vulnerable populations.

BACKGROUND: Biomarkers of carotid atherosclerosis range from those that are widely available and relatively simple to measure such as serum cholesterol levels, and B-mode Ultrasound measurement of intima media thickness (IMT) to those that are more complex and technologically demanding but perhaps potentially more sensitive and specific to disease such as total plaque volume and total plaque area measured from 3-dimensional ultrasound images. In this study we measured and compared intima media thickness (IMT), total plaque volume (TPV) and total plaque area (TPA) in two separate populations, both vulnerable to carotid atherosclerosis. METHODS: In total, 88 subjects (mean age 72.8) with carotid stenosis of at least 60%, based on a peak Doppler flow, and 82 subjects (mean age 60.9) with diabetic nephropathy were assessed in a cross-sectional study. Conventional atherosclerotic risk factors were examined and the associations and correlations between these and carotid ultrasound phenotypes measured from B-mode and 3-dimensional ultrasound images were assessed. RESULTS: IMT and TPV were only modestly correlated in the two separate populations (r = .6, p < .01). ANOVA analyses indicated that both IMT and TPV were significantly associated with age (p < .001) and Framingham score (p < .05), but only TPV was associated with diabetes (p < .001) and presence of plaque ulcerations (p < .01) CONCLUSION: IMT and TPV were modestly correlated in a diabetic patient population and only TPV was associated with diabetes and the presence of plaque ulcerations in a diabetic population and carotid stenosis group. The 3-dimensional information provided by TPV can be critically important in unmasking association with risk factors not observed with less complex single-dimension assessments of carotid atherosclerosis such as those provided by IMT.

Aged↗

PubMed2006

3D prostate model formation from non-parallel 2D ultrasound biopsy images.

Biopsy of the prostate using 2D transrectal ultrasound (TRUS) guidance is the current gold standard for diagnosis of prostate cancer; however, the current procedure is limited by using 2D biopsy tools to target 3D biopsy locations. We propose a technique for patient-specific 3D prostate model reconstruction from a sparse collection of non-parallel 2D TRUS biopsy images. Our method conforms to the restrictions of current TRUS biopsy equipment and could be efficiently incorporated into current clinical biopsy procedures for needle guidance without the need for expensive hardware additions. In this paper, the model reconstruction technique is evaluated using simulated biopsy images from 3D TRUS prostate images of 10 biopsy patients. All reconstructed models are compared to their corresponding 3D manually segmented prostate models for evaluation of prostate volume accuracy and surface errors (both regional and global). The number of 2D TRUS biopsy images used for prostate modeling was varied to determine the optimal number of images necessary for accurate prostate surface estimation.

Adenocarcinoma↗

PubMed2006

Prostate boundary segmentation from ultrasound images using 2D active shape models: optimisation and extension to 3D.

Boundary outlining, or segmentation, of the prostate is an important task in diagnosis and treatment planning for prostate cancer. This paper describes an algorithm based on two-dimensional (2D) active shape models (ASM) for semi-automatic segmentation of the prostate boundary from ultrasound images. Optimisation of the 2D ASM for prostatic ultrasound was done first by examining ASM construction and image search parameters. Extension of the algorithm to three-dimensional (3D) segmentation was then done using rotational-based slicing. Evaluation of the 3D segmentation algorithm used distance- and volume-based error metrics to compare algorithm generated boundary outlines to gold standard (manually generated) boundary outlines. Minimum description length landmark placement for ASM construction, and specific values for constraints and image search were found to be optimal. Evaluation of the algorithm versus gold standard boundaries found an average mean absolute distance of 1.09+/-0.49 mm, an average percent absolute volume difference of 3.28+/-3.16%, and a 5x speed increase versus manual segmentation.

Algorithms↗

PubMed2006

Needle and seed segmentation in intra-operative 3D ultrasound-guided prostate brachytherapy.

In order to guide the needle to the correct location in 3D US-guided brachytherapy, the needle is continuously tracked as it is being inserted. A pre-scan before the needle insertion and a post-scan after the needle insertion are subtracted to obtain a difference image containing the needle. The image is projected along two orthogonal directions approximately perpendicular to the needle, and the 3D needle is reconstructed from the segmented needles in the two projected images. The seeds implanted with the needle are located in the cropped volume along the needle. Thus, the seeds are segmented using a tri-bar model and 3D line segment patterns. Finally, the positions of the seeds are determined using a peak detection technique. Experiments with agar and turkey/chicken phantoms as well as patient data demonstrated that our needle segmentation technique could segment the needle in near real-time with an accuracy of 0.6 mm in position and 1.0 degrees in orientation. The true-positive rate for seed segmentation is 100% for the agar phantom and 93% for the chicken phantom. The average distance to manual seed segmentation was 1.0mm for the agar phantom and 1.7 mm for the chicken phantom.

Algorithms↗

PubMed2006

Relationship of the metabolic syndrome to carotid ultrasound traits.

BACKGROUND: The metabolic syndrome is associated with increased vascular disease risk. We evaluated two carotid ultrasound measurements, namely intima media thickness and total plaque volume, in a Canadian Oji-Cree population with a high metabolic syndrome prevalence rate. METHODS: As part of the Sandy Lake Complications Prevalence and Risk Factor Study, 166 Oji-Cree subjects (baseline metabolic syndrome prevalence, 44.0%, according to the National Cholesterol Education Program Adult Treatment Panel III guidelines) were examined using a high-resolution duplex ultrasound scanner. RESULTS: Image analysis showed that mean intima media thickness was elevated in subjects with the metabolic syndrome (818 +/- 18 vs 746 +/- 20 microm), as was total plaque volume (125 +/- 26 vs 77.3 +/- 17.0 mm3). However, after adjustment for age and sex, the differences were significant only for intima media thickness (P = 0.039). Furthermore, a significant trend towards increased intima media thickness was observed with increasing numbers of metabolic syndrome components: mean intima media thickness was highest among individuals with all five metabolic syndrome components compared to those with none (866 +/- 55 vs 619 +/- 23 microm, P = 0.0014). A similar, but non-significant trend was observed for total plaque volume. CONCLUSION: This is the first study of the relationship between the metabolic syndrome and two distinct carotid ultrasound traits measured in the same individuals. The results suggest that standard intima media thickness measurement shows a more consistent and stronger association with the metabolic syndrome than does total plaque volume.

Adult↗

PubMed2006

Prostate contouring uncertainty in megavoltage computed tomography images acquired with a helical tomotherapy unit during image-guided radiation therapy.

PURPOSE: To evaluate the image-guidance capabilities of megavoltage computed tomography (MVCT), this article compares the interobserver and intraobserver contouring uncertainty in kilovoltage computed tomography (KVCT) used for radiotherapy planning with MVCT acquired with helical tomotherapy. METHODS AND MATERIALS: Five prostate-cancer patients were evaluated. Each patient underwent a KVCT and an MVCT study, a total of 10 CT studies. For interobserver variability analysis, four radiation oncologists, one physicist, and two radiation therapists (seven observers in total) contoured the prostate and seminal vesicles (SV) in the 10 studies. The intraobserver variability was assessed by asking all observers to repeat the contouring of 1 patient's KVCT and MVCT studies. Quantitative analysis of contour variations was performed by use of volumes and radial distances. RESULTS: The interobserver and intraobserver contouring uncertainty was larger in MVCT compared with KVCT. Observers consistently segmented larger volumes on MVCT where the ratio of average prostate and SV volumes was 1.1 and 1.2, respectively. On average (interobserver and intraobserver), the local delineation variability, in terms of standard deviations [Deltasigma = radical(sigma2MVCT-sigma2KVCT)], increased by 0.32 cm from KVCT to MVCT. CONCLUSIONS: Although MVCT was inferior to KVCT for prostate delineation, the application of MVCT in prostate radiotherapy remains useful.

Humans↗

PubMed2006

Prostate segmentation by feature enhancement using domain knowledge and adaptive region based operations.

Estimation of prostate location and volume is essential in determining a dose plan for ultrasound-guided brachytherapy, a common prostate cancer treatment. However, manual segmentation is difficult, time consuming and prone to variability. In this paper, we present a semi-automatic discrete dynamic contour (DDC) model based image segmentation algorithm, which effectively combines a multi-resolution model refinement procedure together with the domain knowledge of the image class. The segmentation begins on a low-resolution image by defining a closed DDC model by the user. This contour model is then deformed progressively towards higher resolution images. We use a combination of a domain knowledge based fuzzy inference system (FIS) and a set of adaptive region based operators to enhance the edges of interest and to govern the model refinement using a DDC model. The automatic vertex relocation process, embedded into the algorithm, relocates deviated contour points back onto the actual prostate boundary, eliminating the need of user interaction after initialization. The accuracy of the prostate boundary produced by the proposed algorithm was evaluated by comparing it with a manually outlined contour by an expert observer. We used this algorithm to segment the prostate boundary in 114 2D transrectal ultrasound (TRUS) images of six patients scheduled for brachytherapy. The mean distance between the contours produced by the proposed algorithm and the manual outlines was 2.70 +/- 0.51 pixels (0.54 +/- 0.10 mm). We also showed that the algorithm is insensitive to variations of the initial model and parameter values, thus increasing the accuracy and reproducibility of the resulting boundaries in the presence of noise and artefacts.

Algorithms↗

PubMed2006

Automated localization of implanted seeds in 3D TRUS images used for prostate brachytherapy.

An algorithm has been developed in this paper to localize implanted radioactive seeds in 3D ultrasound images for a dynamic intraoperative brachytherapy procedure. Segmentation of the seeds is difficult, due to their small size in relatively low quality of transrectal ultrasound (TRUS) images. In this paper, intraoperative seed segmentation in 3D TRUS images is achieved by performing a subtraction of the image before the needle has been inserted, and the image after the seeds have been implanted. The seeds are searched in a "local" space determined by the needle position and orientation information, which are obtained from a needle segmentation algorithm. To test this approach, 3D TRUS images of the agar and chicken tissue phantoms were obtained. Within these phantoms, dummy seeds were implanted. The seed locations determined by the seed segmentation algorithm were compared with those obtained from a volumetric cone-beam flat-panel micro-CT scanner and human observers. Evaluation of the algorithm showed that the rms error in determining the seed locations using the seed segmentation algorithm was 0.98 mm in agar phantoms and 1.02 mm in chicken phantoms.

Algorithms↗

PubMed2005

Disparate associations of a functional promoter polymorphism in PCK1 with carotid wall ultrasound traits.

BACKGROUND AND PURPOSE: Cytosolic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32), encoded by PCK1, catalyzes the first committed step in gluconeogenesis. We previously showed that a -232C>G promoter polymorphism within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription results in loss of negative regulation by insulin, contributing to worsened metabolic control in the context of insulin resistance. We hypothesized that this polymorphism would be associated with carotid atherosclerosis in a sample of 150 aboriginal Canadians. METHODS: Dependent variables were 2 distinct carotid traits, namely intima-media thickness (IMT) assessed using B-mode ultrasound and total carotid plaque volume (TPV) assessed using 3D ultrasound. RESULTS: Multivariate analysis showed significant but opposite associations of PCK1 genotype with these traits. Specifically, subjects with the PCK1-232G/G genotype had more carotid IMT (0.80+/-0.02 versus 0.73+/-0.03 mm; P=0.007) but less TPV (0.10+/-0.09 versus 0.38+/-0.13; P=0.03) than subjects with other genotypes. CONCLUSIONS: The findings connect the key enzyme in gluconeogenesis with atherosclerosis. The meaning of the opposing associations of PCK1 genotype with IMT and TPV is unclear; more work is required to confirm whether these might be distinct quantitative traits with different biological determinants.

Adolescent↗

PubMed2005

Establishment of a serum tumor marker for preclinical trials of mouse prostate cancer models.

Current prostate cancer research in both basic and preclinical trial studies employ genetically engineered mouse models. However, unlike in human prostate cancer patients, rodents have no counterpart of prostatic-specific antigen (PSA) for monitoring prostate cancer initiation and progression. In this study, we established a mouse serum tumor marker from a mouse homologue of human prostate secretory protein of 94 amino acids (PSP94). Immunohistochemistry studies on different histologic grades from both transgenic and knock-in mouse prostate cancer models showed the down-regulation of tissue PSP94 expression (P < 0.001), the same as for PSA and PSP94 in humans. The presence of mouse serum PSP94 was shown by affinity column and immunoprecipitation purification using a polyclonal mouse PSP94 antibody. A competitive ELISA protocol was established to quantify serum PSP94 levels with a sensitivity of 1 ng/mL. Quantified serum levels of mouse PSP94 ranged from 49.84 ng/mL in wild-type mice to 113.86, 400.45, and 930.90 ng/mL in mouse prostatic intraepithelial neoplasia with microinvasion, well differentiated, moderately differentiated, and poorly differentiated prostate cancer genetically engineered prostate cancer mice, respectively (P < 0.01, n = 68). This increase in serum PSP94 is also well correlated with age and tumor weight. Through longitudinal monitoring of serum PSP94 levels of castrated mice (androgen ablation therapy), we found a correlation between responsiveness/refractory prostate tissues and serum PSP94 levels. The utility of mouse serum PSP94 as a marker in hormone therapy was further confirmed by three-dimensional ultrasound imaging. The establishment of the first rodent prostate cancer serum biomarker will greatly facilitate both basic and preclinical research on human prostate cancer.

Animals↗

PubMed2005

3D ultrasound measurement of change in carotid plaque volume: a tool for rapid evaluation of new therapies.

BACKGROUND AND PURPOSE: New therapies are being developed that are antiatherosclerotic but that lack intermediate end points, such as changes in plasma lipids, which can be measured to test efficacy. To study such treatments, it will be necessary to directly measure changes in atherosclerosis. The study was designed to determine sample sizes needed to detect effects of treatment using 3D ultrasound (US) measurement of carotid plaque. METHODS: In 38 patients with carotid stenosis >60%, age+/-SD 69.42+/-7.87 years, 15 female, randomly assigned in a double-blind fashion to 80 mg atorvastatin daily (n=17) versus placebo (n=21), we measured 3D plaque volume at baseline and after 3 months by disc segmentation of voxels representing carotid artery plaque, after 3D reconstruction of parallel transverse duplex US scans into volumetric 3D data sets. RESULTS: There were no significant differences in baseline risk factors. The rate of progression was 16.81+/-74.10 mm3 in patients taking placebo versus regression of -90.25+/-85.12 mm3 in patients taking atorvastatin (P<0.0001). CONCLUSIONS: 3D plaque volume measurement can show large effects of therapy on atherosclerosis in 3 months in sample sizes of approximately 20 patients per group. Sample sizes of 22 per group would be sufficient to show an effect size of 25% that of atorvastatin in 6 months. This technology promises to be very useful in evaluation of new therapies.

Aged↗

PubMed2005

A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model.

Prostate cancer is the most common cancer in adult men in North America. Preclinical studies of prostate cancer employ genetically engineered mouse models, because prostate cancer does not occur naturally in rodents. Widespread application of these models has been limited because autopsy was the only reliable method to evaluate treatment efficacy in longitudinal studies. This article reports the first use of three-dimensional ultrasound microimaging for measuring tumor progression in a genetically engineered mouse model, the 94-amino acid prostate secretory protein gene-directed transgenic prostate cancer model. Qualitative comparisons of three-dimensional ultrasound images with serial histology sections of prostate tumors show the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. Ultrasound imaging identified tumors ranging from 2.4 to 14 mm maximum diameter. The correlation coefficient of tumor diameter measurements done in vivo with three-dimensional ultrasound and at autopsy was 0.998. Prospective tumor detection sensitivity and specificity were both >90% when diagnoses were based on repeated ultrasound examinations done on separate days. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated volume doubling times of 5 and 13 days for two prostate tumors. Compared with other microimaging and molecular imaging modalities, the application of three-dimensional ultrasound imaging to prostate cancer in mice showed advantages, such as high spatial resolution and contrast in soft tissue, fast and uncomplicated protocols, and portable and economical equipment that will likely enable ultrasound to become a new microimaging modality for mouse preclinical trial studies.

Adenocarcinoma↗

PubMed2005

Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models.

Liver metastasis is a clinically significant contributor to the mortality associated with melanoma, colon, and breast cancer. Preclinical mouse models are essential to the study of liver metastasis, yet their utility has been limited by the inability to study this dynamic process in a noninvasive and longitudinal manner. This study shows that three-dimensional high-frequency ultrasound can be used to noninvasively track the growth of liver metastases and evaluate potential chemotherapeutics in experimental liver metastasis models. Liver metastases produced by mesenteric vein injection of B16F1 (murine melanoma), PAP2 (murine H-ras-transformed fibroblast), HT-29 (human colon carcinoma), and MDA-MB-435/HAL (human breast carcinoma) cells were identified and tracked longitudinally. Tumor size and location were verified by histologic evaluation. Tumor volumes were calculated from the three-dimensional volumetric data, with individual liver metastases showing exponential growth. The importance of volumetric imaging to reduce uncertainty in tumor volume measurement was shown by comparing three-dimensional segmented volumes with volumes estimated from diameter measurements and the assumption of an ellipsoid shape. The utility of high-frequency ultrasound imaging in the evaluation of therapeutic interventions was established with a doxorubicin treatment trial. These results show that three-dimensional high-frequency ultrasound imaging may be particularly well suited for the quantitative assessment of metastatic progression and the evaluation of chemotherapeutics in preclinical liver metastasis models.

Animals↗

PubMed2005

A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes.

BACKGROUND: Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes. METHODS: The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21-69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol: high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume. RESULTS: At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P < 0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound scans revealed that total plaque volume measurements (P = 0.037), but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels > 0.70 when comparing intima-media thickness measurements for diabetics versus non-diabetics, thousands of study subjects are required. For comparing total plaque volume measurements, only hundreds of study subjects are required. CONCLUSION: The development of atherosclerotic plaque is greater in subjects with diabetes/impaired glucose tolerance. Total plaque volume appears to capture the atherosclerotic disease burden more effectively in subjects with type 2 diabetes, and would be an appropriate outcome measure for studies aimed at changing the diabetic milieu.

Adult↗

PubMed2005

Registration of two-dimensional cardiac images to preprocedural three-dimensional images for interventional applications.

PURPOSE: To evaluate the accuracy and efficiency of rigid-body registration of two-dimensional fast cine and real-time cardiac images to high-resolution and SNR three-dimensional preprocedural reference volumes for application during MRI-guided interventional procedures. MATERIALS AND METHODS: Mutual information (MI) and correlation ratio (CR) similarity measures were evaluated. The dependence of registration accuracy and efficiency on different resolution and SNR parameters, and also on cardiac-phase differences was evaluated in a porcine model. Two-dimensional images were initially misoriented at distances (d) of 2-10 mm, and rotations of +/-5 degrees about all axes. Registration error and computation time were evaluated, and performance was also assessed visually. RESULTS: The maximum registration error using MI (<2.7 mm and <3.6 degrees ) occurred for d = 10 mm, misrotation of +/-5 degrees , and relative SNR = 1. The computation time was 15 seconds for MI and 10 seconds for CR. CONCLUSION: Registration accuracy was not highly dependent on the relative timing, within the cycle, between the two-dimensional and three-dimensional images. Registration using CR was faster than that using MI, although accuracy was marginally higher with MI. J.

Algorithms↗

PubMed2005

3D TRUS guided robot assisted prostate brachytherapy.

This paper describes a system for dynamic intraoperative prostate brachytherapy using 3D ultrasound guidance with robot assistance. The system consists of 3D transrectal ultrasound (TRUS) imaging, a robot and software for prostate segmentation, 3D dose planning, oblique needle segmentation and tracking, seed segmentation, and dynamic re-planning and verification. The needle targeting accuracy of the system was 0.79 mm +/- 0.32 mm in a phantom study.

Algorithms↗

PubMed2005

Differences between carotid wall morphological phenotypes measured by ultrasound in one, two and three dimensions.

Ultrasound measurements are both surrogate markers and risk factors for atherosclerosis end points. Carotid intima-media thickness (IMT) is most commonly used, but ultrasound can also define structures in higher spatial dimensions, such as total plaque area (TPA) and total plaque volume (TPV). Because there are minimal data regarding the relationship between IMT, TPA and TPV, we measured these variables in 272 Oji-Cree subjects. We found pairwise correlations for IMT:TPA, IMT:TPV and TPA:TPV of 0.507, 0.588 and 0.846, respectively (transformed variables, all P <0.0001). In a subset of 168 subjects with complete cardiovascular risk factor data, we performed multivariate regression analysis to identify sources of variation for IMT, TPA and TPV. We found that the ultrasound traits showed different correlations with individual cardiovascular risk factors. In particular, IMT was significantly associated with hypertension, TPA with smoking and plasma cholesterol, and TPV with diabetes. Therefore, these ultrasound measures of carotid artery morphology, while somewhat correlated, likely represent distinctive quantitative traits with different biological determinants, as underscored by different risk factor associations in the multivariate regression analysis. Because the measurements have different implications and determinants, investigators might need to be selective about the particular measurements they choose for specific applications.

Adult↗

PubMed2005

Image-based cardiac gating for three-dimensional intravascular ultrasound imaging.

Three-dimensional (3-D) intravascular ultrasound (US), or IVUS, provides valuable insight into the tissue characteristics of the coronary wall and plaque composition. However, artefacts due to cardiac motion and vessel wall pulsation limit the accuracy and variability of coronary lumen and plaque volume measurement in 3-D IVUS images. ECG-gated image acquisition can reduce these artefacts but it requires recording the ECG signal and may increase image acquisition time. The goal of our study was to reconstruct a 3-D IVUS image with negligible cardiac motion and vessel pulsation artefacts, by developing an image-based gating method to track 2-D IVUS images over the cardiac cycle. Our approach involved selecting 2-D IVUS images belonging to the same cardiac phase from an asynchronously-acquired series, by tracking the changing lumen contour over the cardiac cycle. The algorithm was tested with IVUS images of a custom-built coronary vessel phantom and with patient images. The artefact reduction achieved using the image-gating approach was > 86% in the in vitro images and > 80% in the in vivo images in our study. Our study shows that image-based gating of IVUS images provides a useful method for accurate reconstruction of 3-D IVUS images with reduced cardiac motion artefact.

Algorithms↗