is obtained using magnetic properties of water molecules in humans. MRI images are now widely used as a golden standard along with old tools such as ECG and X-ray. What makes MRI technique feasible is high abundance of water molecules in the living tissues. When the water molecules of such object are placed in high static magnetic field currently used in clinics, approximately 1/1,000,000 of all water molecules contribute to the image formation. Similarly small contribution is typically obtained for other chemical elements in biomolecules of living objects. This explains why only water was used as an imaging agent to date. Ideally, doctors would like to know concentrations of other metabolaites in their patients for proper and more reliable diagnosis. For example, glucose and cholesterol blood level tests are now used to diagnose a variety on biochemical disorders. While this is a tremendous technological improvement compared to 19 century medicine, such tests take time, i.e. they cannot be obtained within minutes in most cases, but more importantly such tests only represent the static snap shot. Obviosuly, human body is a fast changing dynamic system and thus having a wide range of dynamic tests as clinical tools would make a tremednous advantage for fast diagnosis, patient recovery and survival. Professor Weitekamp from California Institute of Technology invented a chemical method of hyperpolarization that utilizies enhanced spin order of parahydrogen gas, This chemically induced hyperpolarization allows using nearly all magnetically active molecule for image formation. This invention allows sensitivity enhancement by 100,000 fold compared to conventional MRI. At VU Insitute of Imaging Science (VUIIS) we apply hyperpolarized contrast agents to MRI and Magnetic Resonance Spectroscopy (MRS) for early tumor detection and monitoring of therapeutic response. At the moment, we actively design research tools allowing us to image novel hyperpolarized contrast agents and their matabolism in tumors. Eventually, this novel technology permits early detection of metabolic disorders (including cancer) at molecular level. This would lead to essentially new vision of many diseases in the 21st century, because it will enable the doctors to look at it at the molecular level, different stages, progression, etc.

Breast Cancer. Currently breast cancer and the malignant tumor response to therapy are primarily diagnosed with physical examination, mammography, Positron Emission Tomorgraphy (PET), Computed Tomography (CT) and magnetic resonance imaging (MRI). Modern clinical imaging techniques have substantial shortcomings, because they all ultimately detect the anatomical size and physiological changes of tissue modification: mammography - different penetration of x-ray in tissues, MRI - different magnetic properties of water in tumor masses. Moreover, PET (the only currently practiced functional imaging), CT and mammography use ionizing rays and radiation. They are relatively inefficient for early detection of breast cancer (1-2 mm in diamater) when it is essentially 100% curable.
The metabolic imbalance in small tumors precedes the formation of large malignant tumor as well as the spread of metastases. Thus, the detection of metabolic disorder in breast tissues would serve as a more efficient tool for early detection of breast cancer before it becomes detectable by mammography and MRI. Moreover, the assessment of metabolic disorders would reduce the need for biopsy, because the benign or malignant tumor differentiation should be already predicted. Hyperpolarized MRI contrast agents will enable noninvasive measurement of regional dynamic metabolic profile in tumors allowing rapid determination of tumor metabolism using fast MR spectral imaging. Using a novel, molecular imaging agents, therapeutic outcomes for patients with cancer will be improved by the advent of more precise methods of in vivo metabolic imaging which extend beyond simple anatomy to achieve accurate quantifiable chemical analysis without biopsy. Hyperpolarized MRI will (i) provide more real time metabolic information, (ii) use no ionizing/radioactive agents, (iii) have significnatly reduced cost, and (iv) require only a few minutes of examination time. Our long-term goal is to improve early diagnosis, therapeutic monitoring and clinical outcome by magnetic resonance molecular imaging of cancer in patients. Currently our work is supported by National Cancer Institute (NCI) and Prevent Cancer Foundation. For more information on development hyperpolarized MR markers for cancer, please, follow the Application Note #21, which we prepared for Cambridge Isotope Lab, the manufacturer of the first metabolic precursor for parahydrogen based hyperpolarized contrast agent succinate. It is available free of charge at CIL web site



Copyright © Eduard Chekmenev 2003-2009