Ovarian cancer is the second most common cancer amongst gynecologic malignancies, and has the highest death rate. Since the majority of ovarian cancer patients (>75%) are diagnosed in the advanced stage with tumor metastasis, chemotherapy is often required after surgery to remove the primary ovarian tumors. In order to quickly assess patient response to the chemotherapy in the clinical trials, two sets of CT examinations are taken pre- and post-therapy (e.g., after 6 weeks). Treatment efficacy is then evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) guideline, whereby tumor size is measured by the longest diameter on one CT image slice and only a subset of selected tumors are tracked. However, this criterion cannot fully represent the volumetric changes of the tumors and might miss potentially problematic unmarked tumors. Thus, we developed a new CAD approach to measure and analyze volumetric tumor growth/shrinkage using a cubic B-spline deformable image registration method. In this initial study, on 14 sets of pre- and post-treatment CT scans, we registered the two consecutive scans using cubic B-spline registration in a multiresolution (from coarse to fine) framework. We used Mattes mutual information metric as the similarity criterion and the L-BFGS-B optimizer. The results show that our method can quantify volumetric changes in the tumors more accurately than RECIST, and also detect (highlight) potentially problematic regions that were not originally targeted by radiologists. Despite the encouraging results of this preliminary study, further validation of scheme performance is required using large and diverse datasets in future.
Fluorescence in situ Hybridization technology is a commonly used tool to detect chromosome aberrations, which are often pathologically significant. Since manual FISH analysis is a tedious and time-consuming procedure, reliable and robust automated image acquisition and analysis are in demand. Under high magnification objective lenses such as 60x and 100x, the depth of field will often be too small and the FISH probes may not always lie in the same focal plane. A statistical variance based automated FISH analysis method is developed in order to address this problem. On a stack of slices at consecutive image planes with a step size d, the statistical variance alone the z-axis is calculated to form a 2-D matrix. Since pixels shift dramatically to high intensity at FISH probe location, the probes will manifest high peak values in the matrix. A computer-aided detection scheme based on top-hat transform is applied to the matrix to detect FISH probe signals. This study demonstrates a simple and robust method for FISH probe detection as well as a way of 2- D representation of 3-D data.
As one of the important components of optical microscopes, the condenser has a considerable impact on system
performance, especially on the depth of field (DOF). DOF is a critical technical feature in cytogenetic imaging that may
affect the efficiency and accuracy of clinical diagnosis. The purpose of this study is to investigate the influence of
microscopic condenser on DOF using a prototype of transmitted optical microscope, based on objective and subjective
evaluations. After the description of the relationship between condenser and objective lens and the theoretical analysis of
the condenser impact on system numerical aperture and DOF, a standard resolution pattern and several cytogenetic
samples are adopted to assess the condenser impact on DOF, respectively. The experimental results of these objective
and subjective evaluations are in agreement with the theoretical analysis and show that, under the specific intermediate
range of condenser numerical aperture ( NAcond ), the DOF value decreases with the increase of NAcond . Although the
above qualitative results are obtained under the experimental conditions with a specific prototype system, the methods
presented in this preliminary investigation could offer useful guidelines for optimizing operational parameters in
cytogenetic imaging.
KEYWORDS: 3D image processing, Visualization, Signal detection, 3D visualizations, Leukemia, Visual analytics, Cancer, Lithium, 3D acquisition, Image analysis
Chromosomal translocation is strong indication of cancers. Fluorescent in situ hybridization (FISH) can effectively detect this translocation and achieve high accuracy in disease diagnosis and prognosis assessment. For this purpose, whole chromosome paint probes are utilized to image the configuration of DNA fragments. Although two-dimensional (2-D) microscopic images are typically used in FISH signal analysis, we present a case where the translocation occurs in the depth direction where two probed FISH signals are overlapped in the projected image plane. Thus, the translocation cannot be identified. However, when imaging the whole specimen with a confocal microscope at 27 focal planes with 0.5-μm step interval, the translocation can be clearly identified due to the free rotation capability by the three-dimensional (3-D) visualization. Such a translocation detection error of using 2-D images might be critical in detecting and diagnosing early or subtle disease cases where detecting a small number of abnormal cells can make diagnostic difference. Hence, the underlying implication of this report suggests that utilizing 3-D visualization may improve the overall accuracy of FISH analysis for some clinical cases. However, the clinical efficiency and cost of using 3-D versus 2-D imaging methods are also to be assessed carefully.
The purpose of this paper is to report a new automatic scanning scheme for high throughput microscopic systems aiming
to facilitate disease diagnosis in genetic laboratories. To minimize the impact of the random vibration and mechanical
drifting of the scanning stage in microscopic image acquisition, auto-focusing operations are usually applied repeatedly
during the scanning process. Such methods ensure the acquisition of well focused images for clinical diagnosis, but are
time consuming. The technique investigated in this preliminary study applies the auto-focusing operations at a limited
number of locations on the slide. For the rest of the imaging field, the focusing position is quickly adjusted through
linear interpolation. In this initial validation study, blood pathological slides containing both metaphase and interphase
cells are scanned. For a selected area of 6.9mm×6.9mm, a number of 2×2, 3×2, 3×3, and 4×4 positions are evenly sampled for auto-focusing operations. Respectively, 25, 29, 40, and 41 clinically meaningful cells are identified for each
sampling scheme. For the specific case investigated, the results demonstrate that the 4 position auto-focusing scheme
could obtain the adequate number of clinically meaningful cells for the diagnosis. The schemes with more auto-focusing
operations provide an option for high reliability diagnosis when clinically necessary. More comprehensive research is
planned, and that may lead to optimal design of trade-off for developing the scanning scheme of the high throughput
microscopic systems.
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