Imaging: To Be in the Know with Every Detail (Part 1)

by Wiebke Heiss / MEDICA.de

Word has it that back in the ancient world those sentenced to death sometimes had been cut open in order to catch a glance of the insides of living men. About 100 years ago, science succeeded to allow this look without hurting people. The discovery of X-rays started a rapid development in medical imaging.15/10/2008

Medicine has a new objective: Physicians are to recognise diseases before they become noticeable through symptoms – with the help of molecular imaging. A tumour, atherosclerosis or dementia - illnesses that may break out some day have developed a lot earlier inside the smallest living units of men - the cells. Scientists are convinced that it is in principal possible to trace back diseases to molecular abnormalities - the goal now is to determine and visualise these faults.

The theory behind the concept: If the molecular deviations are known for, for example, cardiac insufficiency special markers with fluorescent molecules or radiation emitting isotopes could be developed that attach to faulty proteins, mutated genes or diseased tissue. According to the lock-and-key principle the signaling markers accumulate at the system's weak point and are detected by imaging devices from the outside. That way, physician would receive clues on whether a patient is prone to cardiac insufficiency or not.

Paradigm shift: Diseases shall not be given a chance to arise anymore

The German Federal Ministry for Research and medical industry businesses decided last year to invest 900 million Euros in molecular imaging. This marks a paradigm shift in the health care landscape: The human being shall not be repaired by doctors after falling ill anymore - instead of this, diseases shall not be given a chance to arise anymore in the first place. A disease is supposed to be diagnosed as early as possible so that it either does not break out or - if it does - only in an alleviated state.

An analysis introduced by the consultancy Frost & Sullivan in 2008 states that the sector of molecular imaging experiences growth: European molecular imaging markets earned revenues of USD 201.1 million in 2007 and may reach USD 287.5 million in 2014. Siemens, too, is part of opening these markets. „We observe a relatively strong growth of molecular imaging in Germany, especially we observe a backlog in terms of the combination PET/CT. There are also many growth markets in regions of emerging economies such as South East Asia, Russia and Latin America“, Markus Lusser, Vice President Global Sales and Marketing for Molecular Imaging of Siemens in Illinois, USA says.

Tracers for tumors, dementia and heart problems

Three areas are particularly important when it comes down to molecular imaging according to Lusser: Classic diagnostic systems such as positron emission tomography (PET) and spectroscopy to start with. „Also the preclinical phase in research is of importance in order to find more suitable biomarkers.“ The third pillar is concerned with the distribution and delivery of isotopes that have a very short half-life and therefore need to be produced locally. „A lack of suitable laboratories for these tasks exists in many countries.“

Siemens invests especially in tmuor diagnostics and therapy. „Molecular imaging based on PET is extremely heavy on oncology“, Lusser explains. „Therefore, we concentrate on developing new isotopes that may open up new possibilities such as, for example, identifying special tumors that are resistant to radiation therapy.“ Concurrently, Siemens tries to poduce tracers for dementia or a heart tracer that would enable a classification of the myocardal muscle. „This would help the physician to better decide on suitable therapies for the patient.“

- Part 1: To Be in the Know with Every Detail
- Part 2: Of Paying Attention to the Type of Radiation
- Part 3: A Glance Inside and At The Head - fMRT and Portrait Holography

Part 2: Of Paying Attention to the Type of Radiation

Irradiated by Wilhelm Conrad
Röntgen: a woman's hand

Imaging technologies have revolutionised medicine. A little more than a hundred years ago, doctors were still dependent upon physical symptoms mainly on the body's outside for diagnosis. This changed when the German physicist Wilhelm Conrad Röntgen discovered an invisible radiation during an experiment in 1895. A little later the first X-rays in history came into being - such as a radiograph of a woman's hand skeleton that he irradiated for 20 minutes.

Scientists discovered then that this is not very healthy - X-rays can cause cancer. Engineers kept working on the technique and accomplished to reduce the intensity of radiation considerably during the last 30 years. However, some physicians are often still too lax when using radiation: According to the German X-Ray Society half of all X-rays in Germany are unnecessary. Also computer tomography (CT) - an impressive technology that delivers high resolution images from the body's inside and is irreplaceable in the diagnosis of a variety of certain serious diseases - works with X-rays and contributes considerably to the medical over-all exposure to radiation: in 2001, CT examinations made up six percent of all radiological examinations but in the same time were responsible for nearly 50 percent of human's contamination with radiation.

Benefits and risks need to be weighed up

The German Federal Office for Radiation advises an X-ray examination only when the patient benefits from it significantly so that the radition risk seems negligible compared to the benifits of diagnosis. And only when there are no other applications available that could deliver the same diagnostic information.

Other imaging technologies use optical radiation as for example methods that work with infrared light representing a possibility to fill some niches in diagnostics. „Near infrared spectroscopy (NIRS) is not the kind of imaging that produces high resolution images like a CT. It rather creates a surface mapping“, explains Professor Ulrich Dirnagl. The director of the Stroke Centre at the Charité in Berlin examines the oxygenation of the cortex with this method - the outer layer of nerve cells where a lot of sensory and motoric functions are located. Light from the near infrared penetrates tissue very well and is therefore suitable to reach these layers.

Take a look at oxygenation in
the outer layers - with infrared
light; © Dirnagel

It is important to observe oxygenation of the brain since a lack of the gas could cause major damage within minutes. „It is possible to observe and measure brain metabolism in neonates with NIRS“, says Dirnagel. „Another niche could be an examination of soft tissue like the female breast with near infrared light .“ One day it might be feasible to develop a kind of optical mammography. Also molecular imaging could benefit from NIRS because the method could provide new possibilities in finding markers with signaling molecules made of dye that can be detected by near infrared light.

Another application for NIRS maybe in the fight against arthritis: „Near infrared dyes can be injected into the hand joints and a special device can detect when the fluid exits from inflamed joints“, explains Dirnagel. The patient only has to stick its hand inside it and it will be illuminated with near infrared light in order to control progress in therapy. „This all is technically feasible. Now we need to determine whether NIRS is sensitive, specific and worth the money.“

- Part 1: To Be in the Know with Every Detail
- Part 2: Of Paying Attention to the Type of Radiation
- Part 3: A Glance Inside and At The Head - fMRT and Portrait Holography

Part 3: A Glance Inside and At The Head - fMRT and Portrait Holography


Magnetic fields present an important milestone in medical imaging. A very strong magnetic fields is applied to patients with magnetic resonance imaging (MRI). This causes the patient's atomic cores to flip from a low-energy state to a high-energy one. When the magnetic field is switched off the cores fall back into a low-energy state and send out signals that can be detected with highly sensitive antennae. A computer uses the signals to create a tomogram of the body.

MRI is especially well suited for 3D images made from tissue such as soft tissue, organs, articular cartilage, spinal discs and the heart – different to a CT that is better suited for getting a picture of bony structures. A development of MRI resulted in functional MRI (fMRI) that is able to visualise metabolism in the brain - and that way indirectly also human thoughts.

A cup of coffee can tamper results

„fMRI is a gigantic leap for clinical neurological sciences“, says Professor Christoph Stippich, managing senior physician of the Department of Neuroradiology at the University Heidelber. „In Germany, we use fMRI as a real clinical application only in the area of diagnsotics before surgery on brain tumors.“ For example in order to determine how to remove a tumor as gentle and conservative as possible. „An fMRI is of help when the surgeon has to decide how risky the operation will be so that the medical team may only remove part of the tumor and treats the rest with a radiation therapy, for example.“

Neurofunctional imaging techniques have opened up new possibilities in research by observing the brain while it is working. Stippich works on a project with orthopaedics in order to find out how the brain restructures itself after the patient experienced paralysis due to an accident. „In future, fMRI will help to observe reorganisation of the brain“ according to the neuroradiologist. „Questions such as how will the brain react on therapies after a stroke in rehabilitation will be answered. It could be possible to classify patients through an fMRI examination in terms of what therapy will work best for them.“ It will one day be possible to determine how the brain reacts towards damage, how it recovers and what therapy makes most sense at what time in rehabilitation.

There are limitations to this method, though: Since brain function is measured indirectly and those measurements do not concur exactly in neuronal activity a cup of coffee may suffice to tamper results since coffeine influences blood flow. „fMRI is not a perfect technology but in combination with different other technologies such as PET and EEG an extensive picture about varying functions of the brain can be obtained.“

Even the smallest pore is pictured with portrait holography

Something similar is true for a technology whose products keep meeting up with us every day on banknotes and credit cards - holograms. No other imaging techniques is connected to as many mysterious futuristic visions like holography. Though these 3D images are just some kind of special photos in the end - and, additionally, ones that always succeed with a portable device that was developed by Peter Hering. "By using an extremely short recording time of just 35 nanoseconds with a short pulsed laser it is not possible to get a blurred image", explains the managing director of the Institue for Laser Medicine at the University Düsseldorf. The professor is specialised on portrait holography and creates holograms of faces that are very detailed - not even leaving out a single stubble or pore - in 3D.

"In combination with other 3D technologies such as CT and MRI, holograms can accomplish notable things", says Hering. The physicist works on a project that one day may help in forensic science by giving them a better method to identify dead people. "We made a CT and a portrait holography of the heads of 12 caucasian men and 12 caucasian women aged 20 to 25 years and evaluated the data resulting in a determination of the thickness of soft tissue in their faces." When at some point in the future it will become necessary to identify a skull the standardised data from this project may help to create a reconstruction of the dead person near to reality and to determine its identity. "This subject matter is still relevant for the tsunami victims from Phuket. There are still another 4,000 unidentified persons", says Hering.

US American soldiers are supposed to be screened in future

A hologram does not only produce
a 3D image - also the facial
texture with all pores
© Prof Peter Hering

The US army is also interested in Hering's work. When the Ministry of Defence invited Hering to the workshop “The Virtual Face“ the physicist did not know what for. He found out that plans exist to create a whole medical data set of soldiers that are about to go to war. „With the help of high resolution CT and MRI a data set about the inner organs and bones will be created, with the help of holography they want to get an exact image of the face's surface including mimicry", Hering tells. The idea behind it: If something happens to the soldiers while being at war it would one day be possible to 'restore' the soldier by using future technologies such as tissue and nerve engineering. "That sounds like utopia and it certainly will be a much more difficult task than flying to the moon but it is a good idea", says Hering. Thinking about this research being applicable also to civil causes like the treatment of tumor patients and accident victims.

Wiebke Heiss
MEDICA.de

- Part 1: To Be in the Know with Every Detail
- Part 2: Of Paying Attention to the Type of Radiation
- Part 3: A Glance Inside and At The Head - fMRT and Portrait Holography