MedMAX - A beamline for medical research

MedMAX LUND UNIVERSITY | A BEAMLINE FOR MEDICAL RESEARCH

Medical imaging - from atomic to anatomic MedMAX is a unique microscope for medical X-ray imaging, with better resolution and contrast than any other currently existing instrument.

MedMAX will create unique opportunities to visualize the events and processes on a microscopic level that we previously only dreamed about. It will help the research community, including medical students and clinicians, understand what happens in a body with diabetes, improve understanding of brain or vascular diseases and influence the development of innovative new cancer treatments.

MedMAX will consist of two experimental stations, one for high-resolution imaging and one aimed at the study of entire organs or even small animals. MedMAX will be one of 25 beamlines at the X-ray research facility MAX IV in Lund, Sweden, which is currently under construction. Lund University’s existing imaging facilities, including Lund University Bioimaging Center, will complement operations at MedMAX and help ensure its success.

MAX IV‘s revolutionary accelerator technology will change the way we see the world, including how we use visualization in medical research.

The MAX IV facility represents the largest investment ever in research infrastructure in Scandinavia.

MAX IV is being built by Lund University with support from, among others, Knut and Alice Wallenberg Foundation, twelve Swedish Universities, Vetenskapsrådet and in close cooperation with other Swedish and international partners.

The facility will be inaugurated in the summer of 2016 and is adjacent to Lund University, Skåne University Hospital, Science Village Scandinavia, the innovation parks Medicon Village and Ideon, and the upcoming European Spallation Source, ESS. The Öresund region has a unique breadth and depth in medical research within various biotechnology and pharmaceutical companies, which facilitates the development and transfer of world-leading research into medical practice with global impact.

”MedMAX’s unique design differentiates it from all other medical research beamlines. It will be the test-bed for new concepts in therapy and drug invention, new imaging and advanced instrumentation for imaging and detectors, fundamental understanding of biomedical problems and for the dynamics of drug delivery.” William Thomlinson, expert in medical X-ray imaging

”With MAX IV the pharmaceutical industry will get totally new conditions in order to design new medicines with better accuracy and performance. It will also influence the development process as such for new drugs, and may also result in a lower development cost than today.” Sarah Fredriksson, CEO, Genovis

An investment with a potential to make change WHY MEDMAX IS NEEDED MedMAX will use, amongst other techniques, phase contrast imaging techniques in addition to elemental analysis and will allow for exploration of the effects of radiation. Phase contrast is far superior to traditional absorption imaging when used for studying subtle changes in tissues during diseases such as cancer, Alzheimer’s, Parkinson’s and osteoporosis. The technique is also well suited for improving our knowledge and treatment of teeth, and the interface between bone tissue and implants.

With elemental analysis the presence of specific substances in biological samples can be detected and quantified, including uptake and distribution of pharmaceuticals or toxic substances.

This can also give us insights into disease processes at cellular level, such as stem cells and their capabilities, regeneration of myocardial tissue at infarcts, nerve injuries and neuropathy, and knowledge about asthma, COPD and other lung diseases.

Several research groups, both in Lund as well as internationally, are close to major breakthroughs in these areas.

In order to take the next step in this research development - and really make the breakthroughs that lead to better and earlier diagnosis or ability to delay and cure diseases

- sophisticated methods and instruments are needed.

MedMAX is such an instrument – an advanced imaging facility with the capability to understand, explain and improve the lives of people.

WHAT WE CAN DO WITH MEDMAX The brightness of the X-rays at the MedMAX experiment stations will provide world-leading precision, both in terms of localization and contrast. MedMAX combines imaging in two and three dimensions and you can see how things evolve over time. Add resolution and soft tissue contrast that is unparalleled in the world and you have the recipe for outstanding success.

BUDGET MEDMAX: - Construction of the beamline: 130 MSEK - Research school for some 20 PhD students: 5 MSEK - Strategic recruitment of two professors: 10 MSEK

”MedMAX is an instrument using the most brilliant X-rays you can create on earth. The technology is a significant progress where we with refined techniques can study disease processes with far better image resolution. MedMAX will give us researchers and clinicians totally new opportunities to do front line research.” Kristina Lång, MD, Medical Radiology Unit, Skåne University Hospital

WORLD-CLASS RESEARCH Lund University is ranked as one of the top 100 universities in the world and one of the foremost research-intensive universities in Scandinavia. Our 47 000 students, almost 3 000 researchers and 650 professors at eight faculties conduct world-class research in fields including medicine, materials science and sustainable development.

In Lund, diversity comes together with some of the sharpest brains of our day in a research and education environment that forms a hotbed for scientific breakthroughs. Together we all work to understand, explain and improve our world and the human condition.

YOUR GIFT MAKES A DIFFERENCE When you choose to support MedMAX at Lund University, you become part of our shared search for knowledge. At Lund University you can always find fields or disciplines close to your heart, whether it is a question of creating a sustainable society or finding the key to a specific disease. We work with you to tailor your giving so that you know exactly where the money goes and what we have achieved with your help.

MORE INFORMATION ABOUT MEDMAX Martin Bech, +46 46-17 85 42, Martin.Bech@med.lu.se Tomas Lundqvist, +46 70-846 76 88, Tomas.Lundqvist@maxlab.lu.se Web: www.maxlab.lu.se/medmax CONTACT THE DEVELOPMENT OFFICE Ulrika Nilsson, +46 46-222 34 39, ulrika.nilsson@rektor.lu.se

LUND UNIVERSITY Box 117 221 00 Lund Tel +46 46-222 00 00 http://www.lunduniversity.lu.se /giving-to-lund

Photo: Gunnar Menander, Kennet Ruona, Franz Pfeiffer, Illustration MAX IV: Fojab Arkitekter AB

Lund University - For a better world

Nerve injuries and neuropathy With a new unbeatable imaging technology we will be able to identify how nerve fibers grow in natural and artificial environments and are affected by disease for the best treatment of nerve injuries and neuropathy.

WHY WE NEED MEDMAX Functions in our hands and legs are controlled by electrical signals from the brain and spinal cord that travel out to our muscles via nerve fibres in peripheral nerves. Sensory impulses from our skin travel through other types of nerve fibres to our spinal cord and brain where they can be interpreted. Damage to a peripheral nerve in an adult can lead to permanent disability. Approximately 70,000 new nerve injuries requiring surgical repair and reconstruction occur in the EU each year, which translates into a yearly cost of 2.2 billion Euro.

Diseases can also cause reduced function in peripheral nerves, otherwise known as neuropathy. One example is diabetes, where patients suffering from neuropathy can develop sores on their feet, and risk amputation as a result.

Following extensive nerve damage, in which a defect between the damaged nerve ends has occurred, the defect can be bridged with various types of ‘spare parts’.

One such spare part is a biodegradable tube, which is made from biological or artificial structures and loaded with special components and cells that stimulate damaged nerves to grow over the defect. Another method is to use nerve fibres from deceased humans, where cells are first removed chemically. This creates a good structure for the growing nerve fibres to follow in order to bridge the defect.

WHAT WE CAN DO WITH MEDMAX With the help of MedMAX, researchers can get a three-dimensional image of the repair process following a nerve reconstruction. With MedMAX, researchers can create detailed maps of the processes at work in peripheral nerve trunks affected by neuropathy, and analyse how nerve fibres grow in artificial environments. This will lead to new knowledge of how to develop the best possible treatment for patients with severe injuries.

There are a number of other causes of neuropathy, where the function of both nerve fibres and their insulating cell layers are affected, and therefore at risk of atrophy. The specific mechanisms responsible for the development of neuropathy are not yet known.

MedMAX will give researchers the opportunity to understand the mechanisms involved in neuropathy, which will lead to new treatment methods and medicines designed to help restore nerve function.

Photograph showed with acknowledgement from Prof. Kirsten Haastert-Talini

CONTACT Lars B. Dahlin, Hand Surgery, Lund University

Bone and cartilage degeneration As we are getting older, there will be a need for sustained mobility. Imaging with phase contrast technology provides unprecedented opportunities to study the bone, cartilage, and the sustainability of implanted prosthesis.

WHY WE NEED MEDMAX While it is well known that bone fragility and osteoporosis ultimately lead to bone fracture, the mechanisms contributing to decreased bone quality is still not well understood. In Sweden, every second woman of age 50 or above will suffer from osteoporosis. Due to lack of proper treatment, many women will have life-long problems of reduced mobility and as a consequence a lowered life quality. Bone tissue is well suited to visualization by x-rays at MAX-IV, which will provide important insight into the three-dimensional structures of the micro-impurities that have long been suspected to influence the bone crystal structure, which subsequently leads to decreased bone strength.

WHAT WE CAN DO WITH MEDMAX Studies of the development and growth of bones and cartilage in infants and young people, as well as investigations on cartilage degeneration in the aging population, have attracted a significant amount of research already in the medical research community.

A group in Canada has used phase-contrast techniques for imaging the cartilage in joints and trabecular bone architecture, imaging that is not possible with conventional methods. The development and potential reversal of arthritis as well as the response of bone tissue and structure to external stresses can be studied.

At Lund University there is a tradition of studying specialized tissues such as cartilage, bone, muscle and lung. Therefore there is a great interest in studying structural features including physical properties of the tissue as well as structural changes in diseases affecting the tissue. MedMAX will contribute to this research by providing possibilities of imaging the structural and physical properties in the bone/cartilage and to study the changes caused by diseases. A particular area of interest for studies at MedMAX is how implants are integrated by the surrounding tissue and how this integration can be optimized.

Phase contrast tomography of bone-cartilage interface.

Franz Pfeiffer, Technische Universität, Mßnchen CONTACT Patrik Önnerfjord, Connective Tissue Biology, Lund University

Lung disease COPD Synchrotron radiation provides the opportunity to obtain detailed information about how lung tissue is affected by drugs, which have a great potential for breakthroughs in lung research.

WHY WE NEED MEDMAX Chronic obstructive pulmonary disease, COPD, is one of the major diseases in the western world. In Sweden alone, 500,000–700,000 people suffer from COPD, corresponding to 5–8 percent of the population. Every year approximately 3,000 people die from COPD in Sweden.

COPD is estimated to be the third most common cause of death in a few years. At present time, no cure exists.

Treatment only helps to diminish the symptoms and to prevent further development of the disease.

Intensive research is in progress to develop new pharmaceuticals to treat COPD, but it is difficult to study the effect on the lung tissue in detail, both in animal models and in patients. It is hence of great importance to develop new imaging methods to study the effect of a given substance in-vivo with high spacial resolution.

Phase-contrast tomography of microscopic alveolar in the lung. Franz Pfeiffer, Technische Universität, München CONTACT Lars E Olsson, Medical Radiation Physics, Lund University

A large number of researchers are working with COPD, both in the Skåne/Copenhagen region and in the Nordic countries. Hence, Lund is an ideal location for MedMAX where lung tissue can be analysed in three dimensions.

WHAT WE CAN DO WITH MEDMAX With MedMAX the effects of new substances for COPD treatment can be studied with phase-contrast imaging methods to obtain detailed information on the morphological changes in the lung tissue. Complementary to such studies, the equipment within the Lund University Bioimaging Center (LBIC) infrastructure will also be available. At MedMAX the high sensitivity will provide a unique tool to non-invasively follow the impact of disease and drug onto the lung.

In COPD research, imaging methods already play a crucial role, but the advanced imaging methods accessible at MedMAX would provide additional unique information. In the field of drug development for lung diseases, there is a great need for MedMAX and there is a potential for a breakthrough in identifying good treatment substances and strategies.

Inner ear dysfunction Nestled in the complex inner ear there are sensory receivers and signal systems for hearing and balance, for which synchrotron imaging provide new opportunities of identification and studies.

WHY WE NEED MEDMAX The inner ear dwells deep inside the skull and is extremely difficult to study in vivo with conventional imaging methods. The inner ear labyrinth has liquid filled compartments separated by membranes. Some compartments are rich in potassium, whereas the surrounding spaces have potassium levels similar to the usual extracellular fluid.

The function of the ear relies on right potassium levels in these fluids.

Disorders of the inner ear cause hearing loss, deafness, tinnitus and balance disturbances. Hearing problems are major communicative problems in the population. Although recent developments of hearing aids and implantable device provide some relief, there are few treatments for the causes, believed to rise from an abnormal change in potassium concentration in the inner ear compartments.

Balance disorders cause both acute symptoms of dizziness and chronic balance disturbances leading to fall and fractures.

WHAT WE CAN DO WITH MEDMAX The range of imaging methods in Lund will be expanded when MedMAX comes in action and we hope to be able to develop techniques to visualize the inner ear compartments with synchrotron phase-contrast X-ray techniques. While providing image-resolution down to the micrometre range (1 micrometre = 0.001 mm), phase-contrast will at the same time providing sufficient sensitivity to quantitatively determine the potassium concentrations in the different compartments of the ear.

X-ray phase-contrast techniques are especially useful when there are fluid surfaces or interfaces, and the inner ear anatomy very much consist of such fluid compartments and function depends on movement of structures within those compartments. We will therefore develop techniques were we actually may visualize hearing happening or balance control take place, as well as changes due to disease and effects of manipulating the inner ear signalling.

Research aims at identifying the receptors and signalling system in the inner ear of importance for sound or balance stimulus. At the time being phase-contrast x-ray techniques at MedMAX are the best candidates to be adopted and developed to visualize changes of fluid contents in the hidden structures of the ear. In combination with human studies, this will shed light on the fundamental functions in hearing and balance and will help understand the mechanisms behind development of inner ear diseases and their treatment.

The inner ear.

Didier Descouens, Wikipedia commons

CONTACT M책ns Magnusson, Ear, nose and throat diseases, Lund university Eva Degerman, Insulin Signal Transduction, Lund university

Cancer and radiobiology World-leading features for imaging enables multi-dimensional images of high resolution - an important weapon against cancer.

WHY WE NEED MEDMAX Radiation therapy is one of our best weapons in the fight against cancer and approximately every second cancer patient undergoes radiation therapy. Through significant technical and physical method development radiation therapy is now highly refined. The effect of the therapy can largely be limited to the tumour region and hence negative effects of the therapy can be minimised.

Despite these developments, some tumours, such as severe brain tumours or lung cancer, can still not be successfully treated. There are possibilities to have a more successful treatment of the complicated tumour cases, but that requires an increased knowledge about the radio-biological effects on cellular level and the effect on organ and body functions.

Phase contrast tomography of rat brain.

Franz Pfeiffer, Technische Universität, München CONTACT Crister Ceberg and Bo-Anders Jönsson, Medical Radiation Physics, Clinical Sciences, Lund University

WHAT WE CAN DO WITH MEDMAX The synchrotron radiation at MedMAX will deliver a highly defined beam.

Combined with MedMAX’s world leading properties of imaging in 2D and 3D with high resolution and high contrast in soft tissue, there will be outstanding opportunities to study the radiobiological effect on microscopic level, and how radiation therapy can be used in both conventional radiation therapy and in development of new innovative treatment methods and medicaments. By translation of knowledge from MedMAX to the clinic, this can contribute to a higher curing rate of cancer patients in the future.

Brain diseases Brain researchers will be able to make new discoveries thanks to safe and accurate imaging of disease processes in Alzheimer’s, Parkinson’s and stroke.

WHY WE NEED MEDMAX Changes in the brain are often caused by restricted blood supply (ischemia) or shortage of oxygen (hypoxia). Every year 30 000 swedes are hit by a stroke – which is just one example of such a disease. Early diagnose relies on a clinical examination and imaging of the brain, which allows identification of different types of brain damage. Here the time aspect is of crucial importance – successful treatment relies on early and correct diagnosis. This takes a certain amount of learning as the diagnosis is based on a correlation with tissue analysis by histology. Other brain diseases where both diagnostics and treatment need improvement include Alzheimer’s disease, Parkinson’s disease and brain tumours, which also require tissue biopsies.

Fig. Phase-contrast CT of a tumor bearing rat brain.

Franz Pfeiffer, Technische Universität München.

CONTACT Elisabet Englund, Department of patology, Lund University Gunnar Gouras, Experimental Dementia Research, Lund University

WHAT WE CAN DO WITH MEDMAX Detailed tissue analysis may be done non-destructively with synchrotron radiation, providing a promising tool for 3D investigations of the morphology and function of healthy and diseased tissue. This type of imaging can be done at the MedMAX beamline, hence allowing studies of stroke, brain tumours, slow inflammatory brain diseases and neurodegenerative diseases like Alzheimer, Parkinson etc. MedMAX can thus provide valuable new insight otherwise unavailable by other methods today. This new knowledge is important for helping us to understand the diseases and to evaluate disease development and reactions to new treatment.

This will hopefully lead to the development of improved treatment of multiple brain diseases.

Diabetes There is great potential in gaining new knowledge about diabetes disease mechanisms, using nanoparticles and high resolution images.

WHY WE NEED MEDMAX Diabetes is a disease that highly affects our blood vessels, due to the high concentrations of glucose being spread by the blood vessels into the entire body. In addition, insulin is secreted and delivered to all tissues in the body via our blood vessels.

It is an unsolved challenge to image the interaction between molecules in the blood vessels and cells in various organs like the pancreas, liver, brain and in fat and muscle tissue.

X-ray based micro-angiography is a potentially important tool to investigate the metabolism of glucose in the body.

In this method, nanoparticles coated with signalling molecules, can be directed to the blood vessel system and surrounding tissue. Another important goal in diabetes research is to understand the behaviour of the beta cells in the pancreas at the microscopic level.

WHAT WE CAN DO WITH MEDMAX MedMAX can have a large impact on our understanding and interpretation of how the tissue changes in a body with diabetes.

High contrast imaging can give essential information to help in the understanding of the effect of certain molecules in the blood vessels on the cells in various organs.

Scientists will study different types of tissue to examine neurology, hepatic metabolism, how hormones are secreted, etc.

X-ray based micro-angiography may be used to find ways to prevent diabetes development by genetic, immunological and pharmacological treatments.

With time-resolved phase contrast imaging at MedMAX, researchers will also be able to monitor very small microscopic changes in cells and tissues during stimulation by nutrients or during disruption by disease-causing factors.

The development of such time resolved imaging techniques can provide high resolution movies of disease processes for both type 1 and type 2 diabetes. These movies will provide researchers with the tools to find the very early symptoms of diabetes.

Phase contrast tomography of micro-vascular structures.

Franz Pfeiffer, Technische Universität, München CONTACT Erik Renström, Islet patophysiology, Malmö, Lund University