Abstract: The invention relates to a system for automatically adjusting an exposure time to improve or otherwise optimize a dynamic range of a digital image. The system includes a camera configured to capture an image of a subject within the field of view at a first exposure time. The captured image is composed of multiple pixels, with each pixel having a respective intensity value. The system further includes a shutter or suitable control configured to control an exposure time of the camera. A controller configured to carryout the following steps including: (a) querying a frequency distribution of pixel intensity values; (b) determining an effective “center of mass” of such a distribution, or histogram, to determine an adjusted exposure time; and (c) capturing a second image of the subject at the adjusted exposure time thereby obtaining an image with an improved or optimal dynamic range.

Abstract: Interestingly, for prognosis, the significant biomarkers for Gefitinib-treated GBM patients (RTOG 0211) appeared to differ compared to historical, RT and non-Gefitinib-treated GBM patients. In Gefitinib-treated patients, those with higher levels of nuclear pAKT driven by PTEN loss, higher levels of nuclear pMAPK, and lower levels of nuclear pmTOR had significantly worse clinical outcomes. In contrast, in non-Gefitinib-treated patients, patients with PTEN-deficiency, and higher levels of EGFRvIII, total EGFR, IGFR1, NFkB and lower levels of nuclear Survivin appeared to have adverse clinical outcomes, highlighting the treatment-dependency of these biomarkers.

Abstract: The present invention relates generally to improved methods of defining areas or compartments within which biomarker expression is detected and quantified. In particular, the present invention relates to automated methods for delineating marker-defined compartments objectively with minimal operator intervention or decision making. The method provides for precise definition of tissue, cellular or subcellular compartments particularly in histological tissue sections in which to quantitatively analyzing protein expression.

Abstract: Disclosed herein are methods of identifying suitable patients for postoperative radiotherapy based on the discovery that the quantification of ER, beyond simple positive/negative characterization, can provide valuable predictive information for the treatment of cancer, specifically breast cancer, and more particularly may predict a group more likely to respond to RT and spare patients from a potentially harmful treatment. Furthermore, the true quantification of ER expression provides a continuous recurrence risk assessment for patients being treated with tamoxifen, and therefore the standardization of the data across sites and imaging platforms significantly reduces the misclassification of patients when compared to the current standard by which ER expression is determined.

Abstract: A system and method for automatically and quantitatively determining the optimal dilution of a reagent is provided. In one embodiment, a plurality of dilution sets are received, where each of the dilution sets consist of a different respective dilution value and a respective plurality of immunoassay staining intensity values. A respective dynamic range metric is determining for each of the plurality of dilution sets relative to the respective plurality immunoassay staining intensity values. Having found the respective dynamic range metric, a dilution set having the numerically optimal dynamic range metric is selected and the dilution value of that dilution set is selected as being representative of an optimal dilution level of the reagent for use in a quantitative immunoassay. In one embodiment, a system is provided with a microscope, an image sensor, and processor module configured determine an optimal dilution of a reagent for use in an quantitative immunoassay.

Abstract: Methods and apparatus for standardizing quantitative measurements from a microscope system. The process includes a calibration procedure whereby an image of a calibration slide is obtained through the optics of the microscope system. The calibration slide produces a standard response, which can be used to determine a machine intrinsic factor for the particular system. The machine intrinsic factor can be stored for later reference. In use, images are acquired of a target sample and of the excitation light source. The excitation light source sample is obtained using a calibration instrument configured to sample intensity. The calibration instrument has an associated correction factor to compensate its performance to a universally standardized calibration instrument. The machine intrinsic factor, sampled intensity, and calibration instrument correction factor are usable to compensate a quantitative measurement of the target sample in order to normalize the results for comparison with other microscope systems.

Abstract: Interestingly, for prognosis, the significant biomarkers for Gefitinib-treated GBM patients (RTOG 0211) appeared to differ compared to historical, RT and non-Gefitinib-treated GBM patients. In Gefitinib-treated patients, those with higher levels of nuclear pAKT driven by PTEN loss, higher levels of nuclear pMAPK, and lower levels of nuclear pmTOR had significantly worse clinical outcomes. In contrast, in non-Gefitinib-treated patients, patients with PTEN-deficiency, and higher levels of EGFRvIII, total EGFR, IGFR1, NFkB and lower levels of nuclear Survivin appeared to have adverse clinical outcomes, highlighting the treatment-dependency of these biomarkers.

Abstract: The present invention relates generally to improved methods of defining areas or compartments within which biomarker expression is detected and quantified. In particular, the present invention relates to automated methods for delineating marker-defined compartments objectively with minimal operator intervention or decision making. The method provides for precise definition of tissue, cellular or subcellular compartments particularly in histological tissue sections in which to quantitatively analyzing protein expression.

Abstract: The method of the invention pertains to determining signal transduction activity in a tissue section by immunohistochemistry techniques. The expression level of the receptor of interest is determined as well as the expression levels of one or more effector molecules of the receptor signal transduction pathway. Furthermore a combined ratio of expression levels of effector molecules in subcellular compartments with the receptor expression was found to have prognostic significance.

Abstract: The method of the invention pertains to determining signal transduction activity in a tissue section by immunohistochemistry techniques. The expression level of the receptor of interest is determined as well as the expression levels of one or more effector molecules of the receptor signal transduction pathway. Furthermore a combined ratio of expression levels of effector molecules in subcellular compartments with the receptor expression was found to have prognostic significance.

Abstract: Methods and apparatus for standardizing quantitative measurements from a microscope system. The process includes a calibration procedure whereby an image of a calibration slide is obtained through the optics of the microscope system. The calibration slide produces a standard response, which can be used to determine a machine intrinsic factor for the particular system. The machine intrinsic factor can be stored for later reference. In use, images are acquired of a target sample and of the excitation light source. The excitation light source sample is obtained using a calibration instrument configured to sample intensity. The calibration instrument has an associated correction factor to compensate its performance to a universally standardized calibration instrument. The machine intrinsic factor, sampled intensity, and calibration instrument correction factor are usable to compensate a quantitative measurement of the target sample in order to normalize the results for comparison with other microscope systems.

Abstract: A method and system for automatically evaluating quality of a slide-mounted tissue sample includes receiving a digital image of a magnified portion of the slide-mounted tissue sample. At least one quantitative quality indicator is automatically determined for at least one of the samples, and the digital image of the magnified portion of the sample. Each of the quantitative quality indicators is automatically compared to a respective minimum acceptable quality threshold. The quantitative quality indicators and associated quality thresholds are selected for suitability with an automated quantitative immunoassay. Failure of one or more of the quantitative quality indicators to meet its respective minimum acceptable quality threshold suggests that the sample is unsuitable for subsequent automated pathological evaluation.

Abstract: The method of the invention pertains to determining the signal transduction activity in a tissue section by immunohistochemistry techniques. The expression level of the receptor of interest is determined as well as the expression levels of one or more effector molecules of the receptor signal transduction pathway. Furthermore a combined ratio of expression levels of effector molecules in subcellular compartments with the receptor expression was found to have prognostic significance.

Abstract: The present invention relates generally to improved methods of defining areas or compartments within which biomarker expression is detected and quantified. In particular, the present invention relates to automated methods for delineating marker-defined compartments objectively with minimal operator intervention or decision making. The method provides for precise definition of tissue, cellular or subcellular compartments particularly in histological tissue sections in which to quantitatively analyzing protein expression.

Abstract: Methods and apparatus for standardizing quantitative measurements from a microscope system. The process includes a calibration procedure whereby an image of a calibration slide is obtained through the optics of the microscope system. The calibration slide produces a standard response, which can be used to determine a machine intrinsic factor for the particular system. The machine intrinsic factor can be stored for later reference. In use, images are acquired of a target sample and of the excitation light source. The excitation light source sample is obtained using a calibration instrument configured to sample intensity. The calibration instrument has an associated correction factor to compensate its performance to a universally standardized calibration instrument. The machine intrinsic factor, sampled intensity, and calibration instrument correction factor are usable to compensate a quantitative measurement of the target sample in order to normalize the results for comparison with other microscope systems.

Abstract: A method and system for automatically evaluating quality of a slide-mounted tissue sample includes receiving a digital image of a magnified portion of the slide-mounted tissue sample. At least one quantitative quality indicator is automatically determined for at least one of the samples, and the digital image of the magnified portion of the sample. Each of the quantitative quality indicators is automatically compared to a respective minimum acceptable quality threshold. The quantitative quality indicators and associated quality thresholds are selected for suitability with an automated quantitative immunoassay. Failure of one or more of the quantitative quality indicators to meet its respective minimum acceptable quality threshold suggests that the sample is unsuitable for subsequent automated pathological evaluation.

Abstract: Methods and apparatus for standardizing quantitative measurements from a microscope system. The process includes a calibration procedure whereby an image of a calibration slide is obtained through the optics of the microscope system. The calibration slide produces a standard response, which can be used to determine a machine intrinsic factor for the particular system. The machine intrinsic factor can be stored for later reference. In use, images are acquired of a target sample and of the excitation light source. The excitation light source sample is obtained using a calibration instrument configured to sample intensity. The calibration instrument has an associated correction factor to compensate its performance to a universally standardized calibration instrument. The machine intrinsic factor, sampled intensity, and calibration instrument correction factor are usable to compensate a quantitative measurement of the target sample in order to normalize the results for comparison with other microscope systems.

Abstract: A system and method for automatically and quantitatively determining the optimal dilution of a reagent is provided. In one embodiment of the claimed method, a plurality of dilution sets are received, where each of the dilution sets consist of a different respective dilution value and a respective plurality of immunoassay staining intensity values. A respective dynamic range metric is determining for each of the plurality of dilution sets relative to the respective plurality immunoassay staining intensity values. Having found the respective dynamic range metric, a dilution set having the numerically optimal dynamic range metric is selected and the dilution value of that dilution set is selected as being representative of an optimal dilution level of the reagent for use in a quantitative immunoassay. In one embodiment, a system is provided with a microscope, an image sensor, and processor module configured determine an optimal dilution of a reagent for use in an quantitative immunoassay.

Abstract: Methods and apparatus for standardizing quantitative measurements from a microscope system. The process includes a calibration procedure whereby an image of a calibration slide is obtained through the optics of the microscope system. The calibration slide produces a standard response, which can be used to determine a machine intrinsic factor for the particular system. The machine intrinsic factor can be stored for later reference. In use, images are acquired of a target sample and of the excitation light source. The excitation light source sample is obtained using a calibration instrument configured to sample intensity. The calibration instrument has an associated correction factor to compensate its performance to a universally standardized calibration instrument. The machine intrinsic factor, sampled intensity, and calibration instrument correction factor are usable to compensate a quantitative measurement of the target sample in order to normalize the results for comparison with other microscope systems.

Abstract: The invention relates to a system for automatically adjusting an exposure time to improve or otherwise optimize a dynamic range of a digital image. The system includes a camera configured to capture an image of a subject within the field of view at a first exposure time. The captured image is composed of multiple pixels, with each pixel having a respective intensity value. The system further includes a shutter or suitable control configured to control an exposure time of the camera. A controller configured to carryout the following steps including: (a) querying a frequency distribution of pixel intensity values; (b) determining an effective “center of mass” of such a distribution, or histogram, to determine an adjusted exposure time; and (c) capturing a second image of the subject at the adjusted exposure time thereby obtaining an image with an improved or optimal dynamic range.