What’s the killer app for this technology?
It’s very clear that hyperpolarized gas MRI is poised to play significant role in revolutionizing the practice of pulmonary medicine. But this is also the greatest challenge. Pulmonary medicine today does not use imaging to a great extent, and does not use MRI at all. Thus, for HP gas to truly reach its potential within pulmonary medicine, we must bring together the MRI and pulmonary community. Polarean believes that our approach of making hyperpolarization available for research will begin to drive this transition and position the technology for maximum impact. It is very likely that once this is underway, the major applications will be in imaging of childhood lung diseases where both compliance with pulmonary function tests and avoidance of ionizing radiation are challenges.
Who benefits from this technology, short-term and long-term?
We see the development of hyperpolarized gas MRI as going through three developmental stages. The first stage is in serving the research imaging market with a platform that provides enormous new opportunity in both MRI research and pulmonary research. The second stage, will be a close alignment with respiratory pharmaceutical companies to develop HP 129Xe MRI into a biomarker that can be used in drug development. The third stage will be to work in partnership with academia, pharmaceutical companies and regulatory authorities to establish clinical approval and reimbursement for improved patient care.
What about pharma?
The pharmaceutical industry has long been interested in HP gases as noninvasive biomarkers for evaluation of respiratory therapeutics. However, until now, they have experienced a great challenge in accessing the technology due to prior intellectual property restrictions. Now that Polarean has acquired the technology and is making it broadly available, we anticipate seeing greater pharma participation. A number of Phase II studies using HP 129Xe MRI are underway. As HP 129Xe MRI becomes more broadly accessible, we expect to see pharmaceutical companies incorporat-ing gas MRI more frequently into their clinical trials and as a companion di-agnostic.
What is the intellectual property situation now?
Previously Amersham Health and GE Healthcare exerted strict intellectual property controls over Hyperpolarized gas MRI technology. This has now changed. Polarean has acquired all intellectual property and our view is that the prior restrictions have impeded the progress of the field. Our strong view is that the key to enabling hyperpolarized gases to reach their potential is to enable customers to deploy this technology in their own centers without constraints. This approach much more closely mirrors the way innovative technologies such as MRI have developed in the past.
What are the uses of hyperpolarized gas MRI?
Clearly the most urgent need for this diagnostic technologyis for non-invasive imaging of pulmonary function. This is already emerging. However, 129Xe has unique properties such as solubility and chemical shift that make it uniquely applicable even beyond the lung. Fully exploiting HP 129Xe beyond the lung will require a focus on sensitive coils, novel pulse sequences and novel reconstruction techniques, but this is beginning to happen. Recently, groups have presented results on imaging 129Xe in the heart, brain, and in oncology applications.
What are the top HP 29Xe MRI research sites doing today?
The past decade saw much focus on novel pulse sequences and coils for HP Gas MRI. In recent years, the work has shifted from the refinement of the technology to its clinical use, particularly with a focus on studying therapy response. There is increasing focus on pediatric applications such as cystic fibrosis and childhood asthma, where absence of ionizing radiation has particular value. Many centers are also directing their attentions towards exploiting the really unique properties of 129Xe, like its solubility and chemical shifts. These new applications range from studying atherosclerosis, to fat metabolism.
What personnel are required to operate a polarizer?
A single technically capable person with an associate degree or trade school certification is sufficient. The operation of the polarizer requires operation of valves, and controls, as outlined in detailed instructions. Most operators can be trained within a day. Many sites employ students to operate their polarizers.
What infrastructure is needed to house a polarizer?
The polarizer is roughly the size of a refrigerator on lying on its side. It requires 3-phase electrical power and compressed air. The room must be sufficiently well ventilated to remove the heat generated by the laser and cell heater. The minimum room size is 10ft x 10ft.
Do you have certification to ship to Canada and Europe?
Yes, the polarizer is certified for shipping to Canada and Europe.
What are the consumables used in xenon production?
The polarizer uses a blended mixture of Xe/He/N2, as well as research grade nitrogen, commercial grade nitrogen, and liquid nitrogen. Typically, the nitrogen cylinders last 4-6 months, while liquid nitrogen consumption is 4-5 liters per day when xenon is produced. Of course, the xenon blend is consumed in proportion to the amount of imaging that is done at the site and the volumes administered. A typical tank of xenon blend contains 60-65 liters of useable xenon for imaging.
How much xenon is used per image?
For clinical imaging most sites use between 300 and 1000 ml of xenon per dose delivered to the subject. For preclinical mouse imaging roughly 50-100ml is used per image.
What is the cost of xenon?
Natural abundance xenon costs about $10/liter, and contains 26% of the 129Xe isotope used in MRI. Many groups seek to boost their image signal to noise by using xenon that is enriched in the 129Xe isotope. Enriching xenon to 78% provides a factor of 3 in signal. However, enriched 129Xe is more expensive.
What are the service requirements for a polarizer?
The service requirements are modest, and the polarizer has proven to be quite robust over time. Many technically-oriented sites choose to perform their own service. Polarean provides preventive maintenance agreements. The primary elements of the polarizer that require periodic maintenance are the vacuum pump, laser, heater, temperature monitoring and optical cell.
What other equipment is needed for 129Xe MRI?
Practically any MRI scanner can be used to conduct 129Xe MRI. The scanner must have multi-nuclear capability, and you need a 129Xe transmit/receive coil and associated transmit-receive switch. Both are commercially available.
What MRI pulse sequences are required for 129Xe MRI?
Most pulse sequences are based on fast gradient echo sequences – either cartesian or radial acquisitions. A number of groups in the field have published their sequences and are willing to share the code.
What are the consumables used in xenon delivery?
Typically 129Xe is delivered to subjects in a single use perfluoropolymer dose delivery bags.