Greater cancer detection is possible with 4-D PET image reconstruction

ScienceDaily (June 8, 2011) — A study introduced at SNM's 58th Annual Meeting is advancing a positron emission tomography (PET) imaging method that uses new 4D image reconstruction to achieve the highest diagnostic capability for the detection of cancer. Mounting evidence shows that PET imaging, which provides visual representations of bodily functions, is significantly more sensitive when used with cutting-edge 4D image reconstruction technology that accounts for patient respiration and produces clearer, more easily interpreted images.

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"PET imaging with 4D image reconstruction could potentially help with early cancer detection, which is an imperative in the field of nuclear oncology," says Si Chen, lead author of the study, Johns Hopkins School of Medicine, Baltimore, Md. "The results of this study and our other studies indicate that the sensitivity of small cancer lesion detection for patients will likely benefit from this novel image reconstruction method, which incorporates an accurate and patient-specific respiratory motion estimation algorithm we previously developed. The improved diagnostic accuracy would allow physicians a more informed understanding of a patient's situation in order to provide better treatment planning for the best possible outcome."

The objective of the study was to quantify the improvement of PET image quality using the 4D PET image reconstruction method with respiratory motion compensation compared to a more conventional 3D PET image reconstruction method. The researchers evaluated the image reconstruction methods using the receiver operating characteristic (ROC) methodology, which is based on signal detection theory widely adopted in diagnostic radiology. A ROC curve is a graphical plot of the sensitivity versus specificity for lesion detection based on the reconstructed PET images. Realistically simulated PET images were employed in this evaluation study using the 4D XCAT phantom -- a digital anthropomorphic phantom that realistically models a typical patient's anatomy, respiratory and cardiac motions. A total of twelve spherical tumors of 10mm diameter were planted inside the lungs and liver of the phantom, which was input to realistic simulation of PET data acquisition using another methodology called Monte-Carlo simulation. The simulated PET data were then reconstructed using both imaging reconstruction methods. The researchers used a mathematical observer, i.e., channelized hotelling observer (CHO), to mimic the interpretation of these PET images by human observers.

Using these methodologies, researchers were able to compare the sensitivity and specificity of the two image reconstruction methods and found that the 4D PET image reconstruction method with respiratory compensation improved the detection sensitivity for the cancer lesions in the liver and lungs. This indicates that evaluation of cancer for lesions smaller than 10 millimeters could be enhanced by compensating for respiratory motion with the 4D image reconstruction method.

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Possible new target for sarcoma treatment and prevention

ScienceDaily (May 23, 2011) — Researchers from Mount Sinai School of Medicine have discovered a protein signaling pathway that becomes hyperactivated in human sarcoma cells, suggesting that medications to inhibit this pathway may be effective in the treatment of human sarcomas. The research is published in the current issue of the journal Cancer Cell.

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A team of researchers led by Stuart Aaronson, MD, Jack and Jane B. Aron Professor and Chairman of the Department of Oncological Sciences at Mount Sinai School of Medicine, compared normal human mesenchymal stem cells to human sarcoma cells and found that the sarcoma cells displayed hyperactive signaling along the Wnt pathway -- a complex network of proteins that interact with each other in a highly ordered manner to regulate numerous biological functions of various species.

The hyperactive Wnt signaling increased the growth of several subtypes of human sarcoma cells by increasing the expression of CDC25A, a gene previously shown to be deregulated in various types of cancer. Increased protein levels of CDC25A enhances the rate of cell proliferation, and cancer cells often exhibit very high CDC25A protein levels compared to normal cells.

"The prevalence of Wnt signaling hyperactivity in human sarcoma cells gives researchers a potential new target as they develop medications to target human sarcoma," said Dr. Aaronson.

"Since several cancer types show increased CDC25A levels, it is regarded as a good target to generate therapeutic agents to dampen its functions and thus will be an important candidate in future drug development," said Sapna Vijayakumar, PhD, Instructor of Oncological Sciences, Mount Sinai School of Medicine, who was the first author of the study.

Normal Wnt functioning is critical for maintaining tissue homeostasis. Hyperactive (deregulated) Wnt signaling is reported to be one of the early causes of colon cancer, and it is also implicated in several other cancer types.

In many instances, hyperactive Wnt signaling increases the expression of certain genes that cause the cell to proliferate faster than normal. This uncontrolled proliferation, often accompanied by additional changes in gene or genes independent of Wnt signaling, can transform a normal cell into a cancerous one.

Sarcomas comprise about one percent of all adult cancers, but about 15 percent of all childhood cancers. There are many sarcoma "subtypes" that can arise from a variety of connective tissue structures, including nerves, muscles, joints, bone, fat, and blood vessels. The most frequent location for sarcomas are the limbs, where the majority of the body's connective tissue is located. About 20 percent of sarcomas are curable by surgery, while 30 percent can be cured by surgery with chemotherapy and/or radiation. About 12,000 new cases are diagnosed in the US each year and about 5,000 people die each year from sarcoma.

Sarcomas are subtyped based on where they occur in the body (in the bone, they are called osteosarcoma, in the smooth muscle they are leiomyosarcoma, in the cartilage they are chondrosarcoma, and so on). Studies suggest that even though sarcomas can occur in any part of the body, they commonly arise from the transformation of mesenchymal stem cells.

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