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A novel imaging approach for early detection of prostate cancer based on endogenous zinc sensing.

ABSTRACT: The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy, there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we used endogenous zinc as an imaging biomarker for prostate cancer detection and progression monitoring. We employed a novel fluorescent sensor for mobile zinc (ZPP1) to detect and monitor the development of prostate cancer in a transgenic mouse model of prostate adenocarcinoma, using in vivo optical imaging correlated with biological fluid-based methods. We showed that the progression of prostate cancer could be monitored in vivo judging by the decreasing zinc content in the prostates of tumor-bearing mice in an age-dependent manner. In a novel quantitative assay, we determined the concentration of mobile zinc in both prostate cell lysates and mouse prostate extracts through simple titration of the ZPP1 sensor. Our findings fulfill the promise of zinc-based prostate cancer diagnostics with the prospect for immediate clinical translation.

SUBMITTER: Ghosh SK

PROVIDER: S-EPMC2912945 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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A novel imaging approach for early detection of prostate cancer based on endogenous zinc sensing.

Ghosh Subrata K SK Kim Pilhan P Zhang Xiao-an XA Yun Seok-Hyun SH Moore Anna A Lippard Stephen J SJ Medarova Zdravka Z

Cancer research 20100707 15

The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy, there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we used endogenous zinc as an imaging biomarker for prostate cancer detection and progression monitoring. We employed a novel fluorescent sensor for mobile zinc (ZPP1) to detect and monito ...[more]

PMID: 20610630

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Project description:Early detection is critical for effective management of Alzheimer's disease (AD) and screening for mild cognitive impairment (MCI) is common practice. Among several deep-learning techniques that have been applied to assessing structural brain changes on magnetic resonance imaging (MRI), convolutional neural network (CNN) has gained popularity due to its superb efficiency in automated feature learning with the use of a variety of multilayer perceptrons. Meanwhile, ensemble learning (EL) has shown to be beneficial in the robustness of learning-system performance via integrating multiple models. Here, we proposed a classifier ensemble developed by combining CNN and EL, i.e., the CNN-EL approach, to identify subjects with MCI or AD using MRI: i.e., classification between (1) AD and healthy cognition (HC), (2) MCIc (MCI patients who will convert to AD) and HC, and (3) MCIc and MCInc (MCI patients who will not convert to AD). For each binary classification task, a large number of CNN models were trained applying a set of sagittal, coronal, or transverse MRI slices; these CNN models were then integrated into a single ensemble. Performance of the ensemble was evaluated using stratified fivefold cross-validation method for 10 times. The number of the intersection points determined by the most discriminable slices separating two classes in a binary classification task among the sagittal, coronal, and transverse slice sets, transformed into the standard Montreal Neurological Institute (MNI) space, acted as an indicator to assess the ability of a brain region in which the points were located to classify AD. Thus, the brain regions with most intersection points were considered as those mostly contributing to the early diagnosis of AD. The result revealed an accuracy rate of 0.84 ± 0.05, 0.79 ± 0.04, and 0.62 ± 0.06, respectively, for classifying AD vs. HC, MCIc vs. HC, and MCIc vs. MCInc, comparable to previous reports and a 3D deep learning approach (3D-SENet) based on a more state-of-the-art and popular Squeeze-and-Excitation Networks model using channel attention mechanism. Notably, the intersection points accurately located the medial temporal lobe and several other structures of the limbic system, i.e., brain regions known to be struck early in AD. More interestingly, the classifiers disclosed multiple patterned MRI changes in the brain in AD and MCIc, involving these key regions. These results suggest that as a data-driven method, the combined CNN and EL approach can locate the most discriminable brain regions indicated by the trained ensemble model while the generalization ability of the ensemble model was maximized to successfully capture AD-related brain variations early in the disease process; it can also provide new insights into understanding the complex heterogeneity of whole-brain MRI changes in AD. Further research is needed to examine the clinical implication of the finding, capability of the advocated CNN-EL approach to help understand and evaluate an individual subject's disease status, symptom burden and progress, and the generalizability of the advocated CNN-EL approach to locate the most discriminable brain regions in the detection of other brain disorders such as schizophrenia, autism, and severe depression, in a data-driven way.

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A novel imaging approach for early detection of prostate cancer based on endogenous zinc sensing.

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A novel imaging approach for early detection of prostate cancer based on endogenous zinc sensing.

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