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Purpose: To evaluate the performance of lesion volumetry in hepatic CT as a function of various imaging acquisition parameters., Methods: An anthropomorphic abdominal phantom with removable liver inserts was designed for this study. Two liver inserts, each containing 19 synthetic lesions with varying diameter (6-40 mm), shape, contrast (10-65 HU), and both homogenous and mixed-density were designed to have background and lesion CT values corresponding to arterial and portal-venous phase imaging, respectively. The two phantoms were scanned using two commercial CT scanners (GE 750 HD and Siemens Biograph mCT) across a set of imaging protocols (four slice thicknesses, three effective mAs, two convolution kernels, two pitches). Two repeated scans were collected for each imaging protocol. All scans were analyzed using a matched-filter estimator for volume estimation, resulting in 6080 volume measurements across all of the synthetic lesions in the two liver phantoms. A subset of portal venous phase scans was also analyzed using a semi-automatic segmentation algorithm, resulting in about 900 additional volume measurements. Lesions associated with large measurement error (quantified by root mean square error) for most imaging protocols were considered not measurable by the volume estimation tools and excluded for the statistical analyses. Imaging protocols were grouped into distinct imaging conditions based on ANOVA analysis of factors for repeatability testing. Statistical analyses, including overall linearity analysis, grouped bias analysis with standard deviation evaluation, and repeatability analysis, were performed to assess the accuracy and precision of the liver lesion volume biomarker., Results: Lesions with lower contrast and size ≤10 mm were associated with higher measurement error and were excluded from further analysis. Lesion size, contrast, imaging slice thickness, dose, and scanner were found to be factors substantially influencing volume estimation. Twenty-four distinct repeatable imaging conditions were determined as protocols for each scanner with a fixed slice thickness and dose. For the matched-filter estimation approach, strong linearity was observed for all imaging data for lesions ≥20 mm. For the Siemens scanner with 50 mAs effective dose at 0.6 mm slice thickness, grouped bias was about -10%. For all other repeatable imaging conditions with both scanners, grouped biases were low (-3%-3%). There was a trend of increasing standard deviation with decreasing dose. For each fixed dose, the standard deviations were similar among the three larger slice thicknesses (1.25, 2.5, 5 mm for GE, 1.5, 3, 5 mm for Siemens). Repeatability coefficients ranged from about 8% to 75% and showed similar trend to grouped standard deviation. For the segmentation approach, the results led to similar conclusions for both lesion characteristic factors and imaging factors but with increasing magnitude in all the error metrics assessed., Conclusions: Results showed that liver lesion volumetry was strongly dependent on lesion size, contrast, acquisition dose, and their interactions. The overall performances were similar for images reconstructed with larger slice thicknesses, clinically used pitches, kernels, and doses. Conditions that yielded repeatable measurements were identified and they agreed with the Quantitative Imaging Biomarker Alliance's (QIBA) profile requirements in general. The authors' findings also suggest potential refinements to these guidelines for the tumor volume biomarker, especially for soft-tissue lesions.

Fisher information provides a bound on the variance of any unbiased estimate for estimation tasks involving nonrandom parameters. In addition, a Fisher information approximation for ideal-observer detectability has been derived. We adopt and generalize such an approximation to establish a method to assess a system's ability to detect small changes in lesion characteristics. By representing the lesion by a size parameter, the ability to detect small changes can be approximated by a function involving the size difference and the Fisher information. A concept, termed the approximated least required difference (ALRD), is introduced and evaluated as an upper bound for assessing a system's power in size discrimination. We present a simulation study for lung nodules as an example to illustrate such a framework, where the image model incorporates a simulated CT imaging system, a thorax background and parameterized nodules. The noise is assumed to be multivariate Gaussian and the noise power spectrum (NPS) method is used to estimate the covariance matrix for the Fisher information calculation. In addition to bounding performance, our results also provide insights into factors, including nodule characteristics and acquisition parameters, that influence ALRD performance. This framework can be extended to connect other discrimination and estimation tasks, facilitating objective assessment and optimization of quantitative imaging systems.

Context: The use of computer aids has been suggested as a way to reduce interobserver variability that is known to exist in the interpretation of immunohistochemical staining in pathology. Such computer aids should be automated in their usage but also they should be trained in an automated and reproducible fashion., Objective: To present a computer aid for the quantitative analysis of tissue-based biomarkers, based on color content analysis., Design: The developed system incorporates an automated algorithm to allow retraining based on the color properties of different training sets. The algorithm first generates a color palette containing the colors present in a training subset. Based on the palette, color histograms are derived and are used as feature vectors to a pattern recognition system, which returns an output proportional to biomarker continuous expression or a categorical classification. The method was evaluated on a database of HER2/neu digital breast cancer slides, for which expression scores from a pathologist panel were available. The system was retrained and evaluated on different transformations of the database, including compression, blurring, and changes in illumination, to examine its robustness to different imaging conditions frequently met in digital pathology., Results: Results showed high agreement between the results of the algorithm and the truth from the pathologist panel as well as robustness to image transformations., Conclusions: The results of the study are encouraging for the potential of this method as a computer aid to assess biomarker expression in a consistent and reproducible manner.

This work is a part of our more general effort to probe the interrelated factors impacting the accuracy and precision of lung nodule measurement tasks. For such a task a low-bias size estimator is needed so that the true effect of factors such as acquisition and reconstruction parameters, nodule characteristics and others can be assessed. Towards this goal, we have developed a matched filter based on an adaptive model of the object acquisition and reconstruction process. Our model derives simulated reconstructed data of nodule objects (templates) which are then matched to computed tomography data produced from imaging the actual nodule in a phantom study using corresponding imaging parameters. This approach incorporates the properties of the imaging system and their effect on the discrete 3-D representation of the object of interest. Using a sum of absolute differences cost function, the derived matched filter demonstrated low bias and variance in the volume estimation of spherical synthetic nodules ranging in density from -630 to +100 HU and in size from 5 to 10 mm. This work could potentially lead to better understanding of sources of error in the task of lung nodule size measurements and may lead to new techniques to account for those errors.

Lung nodule volumetry is used for nodule diagnosis, as well as for monitoring tumor response to therapy. Volume measurement precision and accuracy depend on a number of factors, including image-acquisition and reconstruction parameters, nodule characteristics, and the performance of algorithms for nodule segmentation and volume estimation. The purpose of this article is to provide a review of published studies relevant to the computed tomographic (CT) volumetric analysis of lung nodules. A number of underexamined areas of research regarding volumetric accuracy are identified, including the measurement of nonsolid nodules, the effects of pitch and section overlap, and the effect of respiratory motion. The need for public databases of phantom scans, as well as of clinical data, is discussed. The review points to the need for continued research to examine volumetric accuracy as a function of a multitude of interrelated variables involved in the assessment of lung nodules. Understanding and quantifying the sources of volumetric measurement error in the assessment of lung nodules with CT would be a first step toward the development of methods to minimize that error through system improvements and to correctly account for any remaining error.

Rationale and objectivesTumor volume change has potential as a biomarker for diagnosis, therapy planning, and treatment response. Precision was evaluated and compared among semiautomated lung tumor volume measurement algorithms from clinical thoracic computed tomography data sets. The results inform approaches and testing requirements for establishing conformance with the Quantitative Imaging Biomarker Alliance (QIBA) Computed Tomography Volumetry Profile.Materials and methodsIndustry and academic groups participated in a challenge study. Intra-algorithm repeatability and inter-algorithm reproducibility were estimated. Relative magnitudes of various sources of variability were estimated using a linear mixed effects model. Segmentation boundaries were compared to provide a basis on which to optimize algorithm performance for developers.ResultsIntra-algorithm repeatability ranged from 13% (best performing) to 100% (least performing), with most algorithms demonstrating improved repeatability as the tumor size increased. Inter-algorithm reproducibility was determined in three partitions and was found to be 58% for the four best performing groups, 70% for the set of groups meeting repeatability requirements, and 84% when all groups but the least performer were included. The best performing partition performed markedly better on tumors with equivalent diameters greater than 40 mm. Larger tumors benefitted by human editing but smaller tumors did not. One-fifth to one-half of the total variability came from sources independent of the algorithms. Segmentation boundaries differed substantially, not ony in overall volume but also in detail.ConclusionsNine of the 12 participating algorithms pass precision requirements similar to what is indicated in the QIBA Profile, with the caveat that the present study was not designed to explicitly evaluate algorithm profile conformance. Change in tumor volume can be measured with confidence to within ±14% using any of these nine algorithms on tumor sizes greater than 10 mm. No partition of the algorithms was able to meet the QIBA requirements for interchangeability down to 10 mm, although the partition comprising best performing algorithms did meet this requirement for a tumor size of greater than approximately 40 mm.

Rationale and Objectives: Quantifying changes in lung tumor volume is important for diagnosis, therapy planning, and evaluation of response to therapy. The aim of this study was to assess the performance of multiple algorithms on a reference data set. The study was organized by the Quantitative Imaging Biomarker Alliance (QIBA).Materials and Methods: The study was organized as a public challenge. Computed tomography scans of synthetic lung tumors in an anthropomorphic phantom were acquired by the Food and Drug Administration. Tumors varied in size, shape, and radiodensity. Participants applied their own semi-automated volume estimation algorithms that either did not allow or allowed post-segmentation correction (type 1 or 2, respectively). Statistical analysis of accuracy (percent bias) and precision (repeatability and reproducibility) was conducted across algorithms, as well as across nodule characteristics, slice thickness, and algorithm type.Results: Eighty-four percent of volume measurements of QIBA-compliant tumors were within 15% of the true volume, ranging from 66% to 93% across algorithms, compared to 61% of volume measurements for all tumors (ranging from 37% to 84%). Algorithm type did not affect bias substantially; however, it was an important factor in measurement precision. Algorithm precision was notably better as tumor size increased, worse for irregularly shaped tumors, and on the average better for type 1 algorithms. Over all nodules meeting the QIBA Profile, precision, as measured by the repeatability coefficient, was 9.0% compared to 18.4% overall.Conclusion: The results achieved in this study, using a heterogeneous set of measurement algorithms, support QIBA quantitative performance claims in terms of volume measurement repeatability for nodules meeting the QIBA Profile criteria. [ABSTRACT FROM AUTHOR]

Background: With the emerging role of digital imaging in pathology and the application of automated image-based algorithms to a number of quantitative tasks, there is a need to examine factors that may affect the reproducibility of results. These factors include the imaging properties of whole slide imaging (WSI) systems and their effect on the performance of quantitative tools. This manuscript examines inter-scanner and inter-algorithm variability in the assessment of the commonly used HER2/neu tissue-based biomarker for breast cancer with emphasis on the effect of algorithm training. Materials and Methods: A total of 241 regions of interest from 64 breast cancer tissue glass slides were scanned using three different whole-slide imagers and were analyzed using two different automated image analysis algorithms, one with preset parameters and another incorporating a procedure for objective parameter optimization. Ground truth from a panel of seven pathologists was available from a previous study. Agreement analysis was used to compare the resulting HER2/neu scores. Results: The results of our study showed that inter-scanner agreement in the assessment of HER2/neu for breast cancer in selected fields of view when analyzed with any of the two algorithms examined in this study was equal or better than the inter-observer agreement previously reported on the same set of data. Results also showed that discrepancies observed between algorithm results on data from different scanners were significantly reduced when the alternative algorithm that incorporated an objective re-training procedure was used, compared to the commercial algorithm with preset parameters. Conclusion: Our study supports the use of objective procedures for algorithm training to account for differences in image properties between WSI systems. [ABSTRACT FROM AUTHOR]

The evaluation of fluorescent in situ hybridization (FISH) images is one of the most widely used methods to determine Her-2/neu status of breast samples, a valuable prognostic indicator. Conventional evaluation is a difficult task since it involves manual counting of dots in multiple images. In this paper, we present a multistage algorithm for the automated classification of FISH images from breast carcinomas. The algorithm focuses not only on the detection of FISH dots per image, but also on combining results from multiple images taken from a slice for overall case classification. The algorithm includes mainly two stages for nuclei and dot detection respectively. The dot segmentation consists of a top-hat filtering stage followed by template matching to separate real signals from noise. Nuclei segmentation includes a nonlinearity correction step, global thresholding to identify candidate regions, and a geometric rule to distinguish between holes within a nucleus and holes between nuclei. Finally, the marked watershed transform is used to segment cell nuclei with markers detected as regional maxima of the distance transform. Combining the two stages allows the measurement of FISH signals ratio per cell nucleus and the collective classification of cases as positive or negative. The system was evaluated with receiver operating characteristic analysis and the results were encouraging for the further development of this method. [ABSTRACT FROM AUTHOR]