Biomedical subjects

James C Lacefield

Publications and source records attributed to James C Lacefield.

9 recordsLinked to original sources

PubMed2006

Evaluation of an algorithm for semiautomated segmentation of thin tissue layers in high-frequency ultrasound images.

An algorithm consisting of speckle reduction by median filtering, contrast enhancement using top- and bottom-hat morphological filters, and segmentation with a discrete dynamic contour (DDC) model was implemented for nondestructive measurements of soft tissue layer thickness. Algorithm performance was evaluated by segmenting simulated images of three-layer phantoms and high-frequency (40 MHz) ultrasound images of porcine aortic valve cusps in vitro. The simulations demonstrated the necessity of the median and morphological filtering steps and enabled testing of user-specified parameters of the morphological filters and DDC model. In the experiments, six cusps were imaged in coronary perfusion solution (CPS) then in distilled water to test the algorithm's sensitivity to changes in the dimensions of thin tissue layers. Significant increases in the thickness of the fibrosa, spongiosa, and ventricularis layers, by 53.5% (p < 0.001), 88.5% (p < 0.001), and 35.1% (p = 0.033), respectively, were observed when the specimens were submerged in water. The intraobserver coefficient of variation of repeated thickness estimates ranged from 0.044 for the fibrosa in water to 0.164 for the spongiosa in CPS. Segmentation accuracy and variability depended on the thickness and contrast of the layers, but the modest variability provides confidence in the thickness measurements.

Algorithms↗

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

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

Three-dimensional ultrasound biomicroscopy for xenograft growth analysis.

We reported the use of high-frequency ultrasound biomicroscopy (UBM) in the quantitative analysis of early tumor growth in mice bearing melanoma xenografts in a noninvasive longitudinal assay. Initially, measurements of tumor width, depth and length were obtained using on-screen UBM calipers in real time and tumor volume was calculated with the standard ellipsoid formula w d l pi/6. We were able to detect initiating minute tumor nodules, with the lower limit of detection at approximately 0.01 mm(3) in volume. Successive parallel cross-sectional UBM images (33 microm step) encompassing the complete length of these tumors were also obtained and reconstructed into 3-D representations. Subsequent segmentational volumetric analysis provided a measure of tumor volume. Volume measurements using the two techniques were highly correlated when all 33 xenografts were studied (r = 0.9813, p < 0.0001) and a lower degree of correlation was measured with a subset of early small tumors (r = 0.7973, n = 16, p = 0.0004). Further analysis demonstrated that 3-D segmentational volumetric analysis yielded volume estimates that were often smaller than the caliper-and-formula calculation for most early developing xenografts. Thus, 3-D UBM imaging and segmentation is expected to be especially valuable for small tumors that were observed to grow in irregular shapes other than ellipsoids.

Animals↗

PubMed2004

Three-dimensional visualization and thickness estimation of aortic valve cusps using high-frequency ultrasound.

High-frequency ultrasound techniques are introduced for three-dimensional imaging and thickness estimation of fresh heart valve cusps. Images of porcine aortic valve specimens were acquired within a 12 x 8 x 8 mm3 volume using a VisualSonics VS40 micro-imaging system operating at a 40 MHz centre frequency. Two image volumes were obtained from each of six left coronary cusps. One volume was acquired with the specimen submerged in distilled water and the second volume was acquired through either Hanks physiologic solution or coronary perfusion solution (CPS). The fibrosa, spongiosa and ventricularis were most readily distinguished when the specimen was imaged in distilled water. Colour thickness maps were computed from B-mode image data, and the mean and standard deviations of the thickness were determined for each cusp. In 11 of 12 trials, the image analysis algorithm yielded valid thickness estimates over greater than 98% of the region examined. Mean thickness estimates obtained with specimens submerged in Hanks solution or CPS ranged from 0.66 to 1.03 mm, and submersion in distilled water increased the mean thickness by 20-40%. This observation suggests that the cusps osmotically absorbed water. Information provided by high-frequency ultrasound is expected be valuable for characterizing the morphological properties of heart valves.

Animals↗

PubMed2004

Comparisons of lesion detectability in ultrasound images acquired using time-shift compensation and spatial compounding.

The effects of aberration, time-shift compensation, and spatial compounding on the discrimination of positive-contrast lesions in ultrasound b-scan images are investigated using a two-dimensional (2-D) array system and tissue-mimicking phantoms. Images were acquired within an 8.8 x 12-mm2 field of view centered on one of four statistically similar 4-mm diameter spherical lesions. Each lesion was imaged in four planes offset by successive 45 degree rotations about the central scan line. Images of the lesions were acquired using conventional geometric focusing through a water path, geometric focusing through a 35-mm thick distributed aberration phantom, and time-shift compensated transmit and receive focusing through the aberration phantom. The views of each lesion were averaged to form sets of water path, aberrated, and time-shift compensated 4:1 compound images and 16:1 compound images. The contrast ratio and detectability index of each image were computed to assess lesion differentiation. In the presence of aberration representative of breast or abdominal wall tissue, time-shift compensation provided statistically significant improvements of contrast ratio but did not consistently affect the detectability index, and spatial compounding significantly increased the detectability index but did not alter the contrast ratio. Time-shift compensation and spatial compounding thus provide complementary benefits to lesion detection.

Algorithms↗

PubMed2002

Examples of design curves for multirow arrays used with time-shift compensation.

The effect of 1.75-D array element height on time-shift compensation is analyzed using a two-dimensional array system and a distributed aberration phantom. The analysis uses hydrophone measurements of transmit beams. The results indicate that, for imaging at 3 MHz through aberration representative of the abdominal wall, similar focus compensation performance can be expected from arrays with element pitches less than or equal to 3.0 mm.

Phantoms, Imaging↗

PubMed2002

Spatial coherence analysis applied to aberration correction using a two-dimensional array system.

Complex degree of coherence functions are computed using synthetic and measured ultrasound data to demonstrate noteworthy aspects of coherence analysis in the context of aberration correction. Coherence functions calculated from synthetic data illustrate the importance of proper normalization of the constituent cross-correlation integrals when weak elements and receiver directivity are significant factors. The synthetic data also show that a spike can occur at the zero-lag position of the coherence function when the signal-to-noise ratio is reduced by element directivity near the edges of a large aperture. The latter observation is confirmed by experimental data acquired through tissue-mimicking distributed aberration phantoms using a low f-number two-dimensional array system. The coherence of data acquired at neighboring elements is not changed by time-shift compensation of transmit and receive focusing, but time-shift compensation does improve the coherence of echoes measured over larger separations. The resulting increase in coherence widths evaluated at levels between 0.2 and 0.5 is correlated with narrower -10 dB and -20 dB effective widths in focuses visualized using single-transmit images. Iterative focus compensation methods may benefit from aberration estimation algorithms that take advantage of these longer-range correlations in random-scattering waveforms.

Artifacts↗