Experts outline pros and cons of functional MR and PET in clinical arena

March 8, 2008

Some tantalizing glimpses into future clinical applications of functional MR and PET imaging were provided at Friday’s New Horizons session.

Some tantalizing glimpses into future clinical applications of functional MR and PET imaging were provided at Friday's New Horizons session.Using innovative sequence design and modern contrast media, most functional methods such as perfusion and diffusion can now be easily integrated into standard MRI protocols. This facilitates a combined assessment in a single exam, said moderator Dr. Marco Essig of the department of radiology at the German Cancer Research Center in Heidelberg. Although MR is still less sensitive than PET, fMRI tools are often used as a comparator for some assessments."The problem with MRI is that conventional imaging is not able to fulfill all the requirements," he said. "Functional MRI combines morphology and physiology/pathophysiology and is a possible solution"Essig listed the indications for perfusion as stroke, oncology (whole body), diseases such as rheumatism, and neurodegenerative diseases. Among the indications for diffusion MRI are neuroimaging research, neurosurgical planning, neurodegenerative diseases, oncology, and stroke.

He also listed the main requirements:

  • rapid, reproducible quantification of the functional data sets
  • comprehensible presentation of the results in an interdisciplinary experimental or clinical context
  • comparison of the acquired data with established methods and building of normal collectives
  • transfer of the results from functional imaging techniques into established or new therapeutic concepts and monitoring strategies

Dr. Frank Berger, a clinical researcher in radiology at the University of Munich, explained that angiogenesis is the hallmark in the pathophysiology of tumor growth and metastases, as well as being the target for many new treatments.

In tumors with a diameter of more than 2 mm, passive diffusion is no longer sufficient to reveal the viability of malignant cells, and neovascularization is a necessity. Tumors beyond the occult stage can activate the "angiogenic switch," he said.There are several vascular treatments of cancer. Anti-angiogenic agents block or inhibit the growth of new blood vessels, while vascular disrupting agents destroy or compromise the function of existing blood vessels by targeting more mature vessels and the vessel wall. They are generally cytotoxic to endothelial cells. Vascular modifying agents, on the other hand, change the vasculature in a way that is favorable for the use of other treatments."A considerable number of new vascular treatments continue to fail at phase III and beyond," Berger said. "There is a need for biomarkers that can improve the selection of candidate therapies. Not every treatment is effective in every person. Also, there is a need for predictive tests that can aid selection of treatment in everyday clinical practice."Angiogenesis is a complex process involving many steps, defying a single-method approach, he said. Studying the individual molecular process requires very sensitive methods, but there is no gold standard and many imaging tests are in the early stages of validation.Berger noted that although CT perfusion is widely available and faster and easier to perform than MR, and quantification is straightforward, the technique suffers from poor anatomical coverage, low sensitivity for detecting current contrast agents, and additional radiation exposure.PET and PET/CT, however, can provide essential information in staging and grading of various tumors, treatment monitoring, and detection of recurrences. PET/CT from the head to the pelvic floor can be obtained in less than 10 minutes, and soon the resolution of PET will increase to 3 to 4 mm, according to Prof. Hans Steinert, a senior physician at the Clinic for Nuclear Medicine, Zurich University Hospital.An exciting area for PET researchers is the development of molecular imaging probes, including specific tracers that can be used to detect hypoxia (fluorine-18 misonidazole) and proliferative activity (F-18 thymidine). Hypoxia and tumor cell proliferation contribute to resistance to radiotherapy in head and neck tumor cells. Currently, assessment of these two tumor characteristics is performed in biopsies using immunohistochemical staining and subsequent analysis.Evaluating new cytotoxic drugs is another emerging field, where early identification of inactive compounds and nonresponding tumors may become feasible."Many more ligands are under development for imaging of angiogenesis, apoptosis, and reporter gene expression," Steinert said.