F.A.

Kuijpers1)

The role of technology in future medical imaging

1)

Philips Medical Systems, Best, the Netherlands.

Technological inventions and developments have created new possibilities and breakthroughs in medical diagnostics. The classic example is the discovery of X-rays by W.C. Roentgen, one hundred years ago. The application and commercial success of new diagnostic methods depends mainly on three primary factors: sensitivity, specificity and cost effectiveness. The first two determine the added clinical value, in comparison with existing methods. Nowadays, much greater importance is attached to cost effectiveness than in the past. This also holds true for diagnostic equipment where, for example, one of the consequences is that price erosion will occur where the functionality of an instrument is not open to further development. Cost effectiveness is enhanced by more efficient data handling in the hospitals, which has become possible through the digitization of diagnostic information. The inevitable integration of medical data also offers other new possibilities, such as the use of pre-operatively acquired images during surgical procedures. This article discusses the possible impact of some important current technological developments on medical imaging. The survey is limited to developments for hospitals, mainly within the product range of Philips Medical Systems. The production volume of medical diagnostic equipment is small when compared with consumer products. Consequently, manufacturers of medical equipment can only investigate a limited number of key technologies for new product developments. For other, related developments, especially in information technology, they rely on what becomes available from others in the market as base technologies. X-ray, CT, ultrasound, nuclear medicine and MRI techniques are used in a wide variety of examinations. The most recent, MRI, was introduced in the early 1980s. Since then, there has been no sign of a new technology with such broad application areas. In this article, a few

examples will be given of emerging imaging modalities which show some promise of special clinical applications. However, major developments are taking place in the existing modalities where components and subsystems can be changed and upgraded to give new functionality. In the cath. lab., interventions are now guided by fluoroscopy, while there are developments towards the use of other modalities, of which some examples will be given. Some remarks are made in the section on Technology for Information Integration regarding modality and diagnostic integration in hospitals, made possible by the application of information technology. Innovations in diagnostic imaging modalities Developments in X-ray, CT, MR and ultrasound In videofluoroscopic X-ray systems, the detector, or rather, the detector chain, embodies the key technology. Although it has already reached a high degree of perfection1, continuous improvements are still increasing the performance of, for example, the image intensifier, which is a critical component in the chain. The CCD (Charge Coupled Device) camera, introduced by Philips Medical Systems as the XTV-8 in 1991, is replacing the pick-up tube and offers significant improvements in image quality. The trend here is towards higher resolution where, for certain applications, 2048 x 2048 pixel matrices will be used. In addition to continuous improvements in the detector chain, there are also radically novel approaches which dispense with the need for an image intensifier and TV camera. For example, selenium is a photoconductor with optimal properties for use in X-ray detectors. The control of this elements properties, however, is difficult. In 1993, after many years of intensive research and development, Philips introduced the Thoravision, a revolutionary design for thorax examinations with superb image quality (Fig. 1). The electrical charge pattern generated in the

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1. Thoravision: the X-ray radiation is detected with a selenium photoconductive layer on a drum.

selenium layer by the incoming X-rays is read out capacitively, and the image is obtained directly in digital format. Attempts are currently being made to apply selenium in a highresolution application, namely mammography. The application of selenium has advantages, but also some drawbacks in the practical realization of systems. It is expected that the next generation of X-ray systems will contain a new type of flat, solid-state detectors. These convert X-ray radiation directly into electrical charges which can be detected and displayed very fast with the so-called active matrix approach. These flat detectors are intended for static and dynamic applications. They have intrinsic advantages with respect to stability and reliability and, due to their compact dimensions, they allow geometrically more attractive system designs.

Considerable effort is now being put into the further development of various types of these solid-state detectors. The most promising is the optical image provided by the Cesium Iodide input screen which is directly detected by a high-resolution amorphous silicon photodiode matrix and a TFT (thin film transistor) array (Fig. 2). In CT, new slip-ring technology has enabled continuous rotation which resulted in the introduction, in the late 1980s, of helical scan CT. Volume scanning became possible through this means. An essential contributing new technology was the new X-ray tube based on liquidmetal-filled, spiral-groove bearings which allow very high continuous power. New applications became possible, such as CT angiography, an area which is still evolving rapidly. Real-time helical CT is a challenge. The large amount of data to be handled in real time requires dedicated hardware and software, which is now steadily improving. Eight, fullyreconstructed 256 x 256 images per second have already been achieved. A key component of the CT scanner is the curved array of discrete X-ray detectors. Xenon gas detectors, which are relatively easy to manufacture, were in use for many years, but many modern scanners use solid-state detectors (single crystal CdWO4 or ceramic Gd2O2S, with photodiodes) which have some inherent advantages such as a higher efficiency in detecting X-ray photons. One of the next developments to be expected is the use of multi-array detectors, i.e. a number of parallel rings of solid-state detectors. This will allow faster volume scanning. Another interesting development is the recent introduction of a mobile CT scanner enabling examinations at the bedside and in emergency rooms (Fig. 3). Cardiac applications require very fast acquisition rates. One CT machine for such applications, originating from the Imatron company, uses a scanning electron beam. Its very high price has inhibited its widespread use. A more cost-effective version might increase the use for cardiac applications. In MR the focus will remain on generalpurpose systems, with specialization added via optional application packages, e.g. for neuro, orthopaedics, mammo and vascular. A major trend in MRI over the years has been the reduction of the image acquisition time while still maintaining sufficient image quality. Stronger and faster gradients, with special MR acquisition methods and very fast reconstruction and processing, have now made interactive MRI feasible. Several images per second can be made and immediately displayed on a screen near the magnet. One method,

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presently in research study, lets the operator interactively navigate through 3-D space, using a mouse, to select the location and orientation of the required slice. Moreover, interactive MRI is a great asset for interventional MRI2. Cardiac examinations are even more demanding, in terms of gradient strength and processing power, and it remains to be seen whether dedicated cardiac systems become a reality. Critical requirements here are real-time imaging of the heart and visualization of the coronary arteries. The major cost component of an MR scanner is the magnet. Large steps have already been taken to reduce the cost of manufacture and operation of the superconducting magnet. Magnets are now available which do not require cryogen, but any further breakthrough, e.g. the use of high critical temperature (Tc) wires, is speculative. Some companies have introduced MRI scanners dedicated to a special application, such as orthopaedics. These systems are lower in cost than general multi-purpose scanners, mainly because they use smaller magnets with lower field strengths. The versatility of the MRI scanner is already

very great. A large variety of acquisition methods exist. But new methods are still being developed, such as perfusion and diffusion imaging. An interesting new field, made possible by these methods, is functional MRI. Although,
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3. Tomoscan M, a mobile CT scanner for use at the bedside and for trauma.

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4. Functional MRI study of the brain. The visual cortex is stimulated with LEDs flashing at 8 Hz. The activation map (in red) is superimposed on an anatomical MR image.

of course, many organs can be studied functionally, the term fMRI is mainly reserved for human brain studies to detect effects of external stimuli, where small contrast changes, caused by fluctuations in blood flow and oxygenation, are observed. Here, advanced subtraction techniques are necessary to detect relevant changes because the effects in the image are small, and even the brain has some internal movements. The technique of fMRI is still in the technical and clinical research phase for human brain mapping studies. In the future, detection of pathologies should be possible (Fig. 4). It is clear that MR technology is still evolving, mostly along established paths, but now and then a new technique or device is unexpectedly invented. A recent example is the proposal to use hyper-polarized noble gases for MRI3. This opens up new MRI application fields such as examination of the lungs. 129Xe and 3He have already been used for imaging4. A specialized field of MR is spectroscopy. With this technique, the concentration of biochemical compounds can be measured, albeit with a rather coarse resolution. Human spectroscopy was begun in the 1980s, using localized spectroscopy to study metabolic changes and to characterize tissues and pathologies. First attempts concentrated on 31P which is essential in energy metabolisms. Later, attention shifted to 1H spectroscopy. The interest also shifted from localized spectroscopy to spectroscopic imaging: images of a specific biochemical compound. An important research field is 1H spectroscopic imaging of the brain. In many cases, deficiencies could be correlated with certain pathologies5. Acquisition techniques and processing methods seem well established now. Spectroscopy is still a major applicational research field in MR, from which some applications in routine clinical practice will eventually evolve. Nowadays, ultrasound is a real-time technique. It has become a very important modality with many applications. Equipment varies greatly in price, but even high-performance systems are still low in cost compared with MRI, CT scanners and large X-ray machines. Ultrasound equipment is used for tissue imaging and velocity detection, such as in blood flow. The transducer or probe which generates the acoustic pulse and receives the echographic signal is a key element. The range of transducers is ever-increasing, and includes probes for insertion in body apertures and examining blood vessels. Transducers are already far advanced but are still the subject of major research and development. One goal is to increase the bandwidth for better axial resolution and

reduction of speckle. In radiology, (curved) linear array transducers are the most commonly used. Now under study are arrays known as 1.5D arrays, consisting of several parallel rows of elements to improve out-of-plane focusing. In the more expensive systems, an important trend is towards earlier digitization in the receiver chain. Digitization of the RF signals received by the separate array elements allows image quality improvement measures, such as the use of digital filters. Solutions to the complex phase aberration problem will also require a digital system. This problem is caused by irregularly shaped layers, such as fat in the abdomen, which have an appreciably different ultrasound velocity. Much R&D effort is being devoted to finding solutions. The number of application areas of ultrasound increases steadily. Examples are the growing interest in breast and prostate examinations. For several years 3-D, or Volume, ultrasound has been under development. Visualization and analysis of tissue volumes promise to yield valuable information. Routine clinical applications are still limited, probably due to the inherent imaging characteristics of ultrasound. Blood flow can be visualized in real time, by utilizing the Doppler effect. In the most common method, Colour Doppler, vessels are assigned colours and are shown as an overlay on the greyscale image. An alternative, timedomain, method is called colour velocity imaging (CVI), a technique pioneered by Philips6, which facilitates the detection of small vessels. An extension of CVI is quantification (CVI-Q), for example, of blood flow volume and vessel wall pulsatility. This application area will undoubtedly grow further, and the possibility of measuring tissue motion might lead to a valuable new diagnostic technique: functional vascular characterization. Imaging during interventions The trend towards less invasive surgery is very strong. For example, surgeons use endoscopes in laparoscopic procedures to guide and apply small surgical instruments through keyhole apertures into the body. Also, X-ray fluoroscopy is used in the cath. lab. to guide the catheter. A promising addition in the cath. lab. is intravascular ultrasound (IVUS). This provides detailed, 3-D information of the internal condition of the blood vessels which greatly assists in determining the best strategy for catheter insertion. It employs a method of relating the endovascular ultrasound image with the topography of the vascular tree. Interventional radiologists use both X-ray

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and ultrasound routinely. Furthermore, with MRI several images per second can be acquired, which is leading to the development of MRI for interventional radiology. Interactive MRI, in particular, is a very helpful tool. Although the absence of ionizing radiation is an important advantage, the question remains whether the interventionalist is willing to stay in the magnetic field for lengthy periods. MR scanners for interventional procedures must have easy access, for which various dedicated magnets have recently been introduced. Philips Medical Systems has developed the new wide-aperture Gyroscan NT, which has very good patient access, while maintaining the advantages of a mature product with high field strength and inherently good signal-to-noise ratio. MR can also be used for the measurement of tissue temperature. An interesting utilization in minimally invasive therapy is now under study: destroying malignant tumours by heat or cold treatment under MR temperature monitoring. Methods which use heat deposition are RF ablation, laser ablation and focused ultrasound. The latter procedure7 is of particular interest because it is completely non-invasive. Cold treatment - so-called cryoablation - is performed with probes cooled with liquid nitrogen. An interesting combination in interventional radiology is the use of MRI with an X-ray C-arm in the same room. Such a combination has just been installed in the RWTH University Hospital in Aachen, Germany. The X-ray C-arm can be used for biopsies, catheter guidance etc., and can serve at this stage as a fall-back system. MRI is used for diagnosis and for following the effects of the therapy. Finally, focused ultrasound will also be an area of investigation. Use of images during surgery Normally, visual references and guidance during surgery are based on X-ray, CT or MR images displayed on the lightbox in the operating theatre. However, technological developments are now enabling more advanced support in the form of image guided surgery. CT and MR can produce complete 3-D imaging through sophisticated processing and display techniques, and pre-operative 3-D images clearly visualize the pathology. To utilize this pre-operative information during, for example neurosurgery, markers on the patients head relate the 3-D image to the actual position, and the corresponding image is displayed on a monitor during surgery. The surgeon uses a navigational tool (pointer), the position of which is detected and superimposed on the displayed image.

These images are of great assistance in the operation, e.g. removal of a tumour. A navigational system introduced by Philips, the EasyGuideTM, locates the pointer optically by detecting and following LEDs on the pointer with two CCD cameras (Fig. 5). The EasyGuide approach still uses images which have been acquired prior to surgery. Thus far, imaging during the operation has been done using a C-arm for X-ray fluoroscopy. A more convenient use of intra-operative imaging is possible if the imaging modality is integrated in the co-ordinate system of the patient. Ultrasound can thus become a perfect tool to update

the pre-operative image data as the operation progresses. Digital data handling in diagnostic systems Many diagnostic systems produce digitized image data. Image processing and analysis in the system can significantly increase the performance and functionality. They may also lead to cost-effective solutions. Three examples of new techniques currently under investigation are given here. Flat X-ray detector. The new flat, solid-state

5. EasyGuide: a navigational system for neurosurgery.

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6. Experimental set-up for DNP enhanced MRI. (Courtesy of A.F. Mehlkopf, Technical University of Delft, Faculty of Applied Physics).

X-ray detector mentioned above will have a resolution of at least 1024 x 1024 pixels for high performance applications. A reasonable yield can only be achieved by allowing some pixel and column defects which will be corrected by interpolation algorithms. Fusing sub-images. In several cases it is necessary to fuse sub-images to a full image: - In X-ray, sub-images are acquired from several CCD cameras, e.g. because large area CCDs have a low yield due to their complexity. - Modern MRI scanners have segmented RF coils and a corresponding number of RF receiver channels and each segment generates a sub-image. - The fusion of sub-images requires image processing routines for translations, rotations and distortion corrections. Noise reduction. Catheterization procedures can take several hours. Fluoroscopic images are therefore obtained with the lowest possible dose, resulting in a high noise level. Catheter guidance is routinely done with X-ray and the contrast medium dose administered should be kept as low as possible. Image processing algorithms will be applied (in real time) to reduce the noise in the fluoroscopic images, enhancing the visibility of the catheter. The procedure can then be carried out using a reduced dose. Computer-aided diagnosis An important and frequently asked question is in how far the computer can assist the physician in detecting relevant image features and help in the diagnosis. Many institutes and companies are addressing this question in various ways. A few examples are: - Automatic recognition and classification of stenoses. Good results have been obtained by first applying conventional pattern recognition routines, followed by refinement with neural networks. - The analysis of mammograms is essential for screening and diagnosis. It is a demanding task, as it involves trying to find low-contrast masses and/or small calcifications. Good progress has been reported, where a level of performance has been reached comparable with that of a trained radiologist. New imaging modalities Major variations in existing modalities Ultrasound is an echographic technique, and images display the echogenic properties of tissues. For many years, attempts have been made to produce tomographic images with transmitted ultrasound. The parameters then displayed are the local refractive index, the

differences in velocity, the frequency shift, or a combination of all three. Up till now, attempts to achieve this have been unsuccessful, but new efforts are being made in mammo applications. Another variation of an existing modality is DNP-enhanced MRI (DNP = Dynamic Nuclear Polarization)8. Here, very low-field strength (10 mT) magnets can be used, thus reducing the cost of the system considerably. Magnetization of the protons is enhanced by EPR (Electron Paramagnetic Resonance). An experimental system at the Technical University in Delft is shown in Figure 6. In theory, enhancement can be considerable - up to a factor of 330 - and in

practice a factor of 35 has already been achieved9. The method requires the injection of free radicals, and much effort is being devoted to making these substances less toxic. DNPMRI gives a greatly enhanced signal-to-noise ratio. Also, the free radicals act as contrast agents, making functional imaging possible, and the lowfield magnet allows an open design suitable for interventional procedures. Modalities based on new techniques Quite a few new methods have been proposed to produce medical images using other physical properties of tissues, of which electric impedance and dielectric characteristics are two examples. However, both have very limited applications. Two other examples of new modalities with a possibly brighter future are described below.

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Optical imaging In turbid media, such as biological tissue, photons are absorbed and widely scattered. The scattering decreases with increasing wavelength. In the far infrared spectrum, however, photons are absorbed by water, and in the visible and ultraviolet spectra by blood haemoglobin and pigments such as melanin. Consequently, the best spectral window for penetration into the body is in the near infrared. With Optical Coherence Tomography10, it is mainly the specularly back-reflected, and therefore still coherent, component of the light that is detected. An image is created by scanning in the lateral directions as well as in depth. This technique, in addition to other methods which make use of the coherence of laser light, has the advantage that the incoherently scattered light is not detected, resulting in an immediate image. The penetration depth, however, is only a few millimetres. Applications of such shallow reflective techniques are, for instance, in dermatological and gynaecological diagnostics. During surgery, such techniques can be useful in accurately determining the pathological tissue to be removed. Transmission Time-Of-Flight methods detect the first arriving, non-scattered or slightly scattered, photons with ultra-fast shutter techniques. Experiments show that objects hidden in a milky solution can be made visible. A few centimetres penetration can be achieved, depending on the shutter time. Recently, more promising methods have been developed which extend the penetration depth, so that transmission through 10 cm of tissue is possible. These methods use the diffusely scattered photons. Breast screening is targeted as the first application, and is now being pursued in several companies and institutes. In order to retrieve image information from scattered light, a possible method is to use a point light source and numerous detectors, which measure the distribution of the scattered light emanating from the turbid medium. Subsequently, the position of the source is changed to another location and the process is repeated. From the average light distribution and the changes of source position, a first order image is reconstructed in a similar manner to that of X-ray tomography. The image obtained is blurred, owing to the diffuse nature of the light. Since the physical process of light diffusion is well described, the image can be deblurred by deconvolution with the known diffusion broadening11. An example of such a sharpened image, obtained from real measurements, is

given in Figure 7, which shows an object of 5 mm diameter embedded in a broadly scattering medium of synthetic material (nylon) with a diameter of 10 cm. The result gives encouragement that this method can be applied in breast screening. Magneto encephalography (MEG) and Magneto cardiography (MCG) These methods rely on the measurements of the changes in the extremely weak biomagnetic fields generated by electrical activity in the brain and heart, respectively. The fields are generated by electrical source currents in nerves and

muscle bundles. Cortical activities produce fields of 10 to 100 femtotesla just outside the body, while the heart emits fields of 20 to 50 picotesla. MEG and MCG use SQUIDs (Superconducting QUantum Interference Devices), which are the most sensitive detectors for magnetic flux. MEG uses low Tc SQUIDs (i.e. operating at liquid helium temperature). Variations of the magnetic field just outside the head are measured at n different points by an n-channel system. A shielded room is necessary to suppress external electrical and magnetic interference. Although the first commercial MEG systems (7-channel) were introduced in the mid 1980s, there are still only a few dozen installed worldwide. Philips research laboratories have installed two systems, in Jena and in Hamburg,

7. Reconstruction from optical imaging measurements on a phantom: a cylinder of 10 cm diameter with tissue-like optical properties and tumourlike inhomogeneity.

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with 19+31 and 31+31 channels, respectively. Systems with more than 100 channels are now currently available for investigational purposes, but application areas are still restricted to the study of epilepsy and brain function. At present, MCG shows more promise and will, presumably, be less expensive. Higher magnetic field strengths mean that greater signal noise can be tolerated and, therefore, high Tc SQUIDs can be used (they only require liquid nitrogen for cooling). Moreover, the shielded room necessary for MEG can be replaced by a much cheaper compensation system. The raw data from MCG look very similar to ECG signals. It is a major problem to reconstruct the local source currents from the raw data. This so-called inverse problem cannot be solved analytically. Reconstructions rely on either of two models: - Single dipole reconstruction. This is based on the assumption that only a single dipole is active at a certain time. MCG can accurately locate the position, amplitude and direction of the dipolar current source. - Multiple dipole reconstruction. Here, the amplitude and direction of the dipole has to be determined in every dipole voxel. This results in a local source current density on a predetermined surface. The reconstructed dipoles or currents have to be related to a morphological image. So far, MRI has been used almost exclusively for this. The clinical added value of MCG, mainly for arrhythmia and myocardial infarction, is the subject of current investigations. Technology for information integration In the foregoing chapters, several examples of the application of Information Technology (IT) for specific purposes have been given, such as the use of pre-operative images during surgery and various kinds of image processing. But it is obvious that IT enables a further-reaching integration of digital data in the hospital environment. In fact, modern networking technology also allows connection to the outside world. Telemedicine and teleradiology have become feasible, and even telesurgery might become possible in the future. In this section, however, only developments inside the hospital will be considered. In the radiology department, dedicated systems (RIS) are now commonly used for administrative purposes. Similar administrative systems will be used in areas such as Cardiology (CIS) and Radio-Oncology. Hospitals have administrative information systems (HIS) which are already partly connected to departmental

systems like RIS, CIS, the laboratory and the pharmacy. Integration of images and other diagnostic information is the next step. In the multi-vendor, multi-modality environment in the hospital, this is a very complicated process. Huge amounts of digitized data from heterogeneous sources have to be handled. Earlier attempts to introduce large networks for Picture Archiving and Communication Systems (PACS) in existing hospitals have not been successful. A bottomup approach, commencing within the departments, turns out to be more realistic. The radiology department, for instance, will soon be transformed into a completely digitized environment to take full advantage of easy and efficient communication, presentation and archiving. A first step is the creation of stand-alone viewing, storage and retrieval stations. The following are two of the many systems already in existence: - Ultrapacs, introduced by Swift Technologies for storing ultrasound images on compact disc. - The CD-Medical Recorder, introduced by Philips in 1995, for storing cardiac cine series on CDs. JPEG data compression is used, with compression factors of 6 to 7, enabling the storage of 3000 images per disc and a retrieval rate of 15 images per second. The CD-Medical Recorder is connected to a CD-Medical View Station which displays the images with the original image quality of the cath. lab. Options for this View Station, such as quantitative analysis, will also be made available (Fig. 8). The next task is the integration of images from various different modalities. The EasyVision CT/MR workstation is designed to receive data from multiple scanners without interrupting examinations. This workstation is capable of CT/MR image matching and has extensive 3-D functionality, such as multiplanar reformatting and advanced visualization techniques. These multi-modality review stations will further develop in functionality and performance and will become valuable tools for the radiologist, even in making an initial diagnosis. Procedures will be guided by software developed from clinical practice. A necessary condition is the use of high-resolution (2048 x 2048) black and white monitors, which are not available in the consumer world and are only developed for specialized professional use. A useful addition to these workstations will be voice recognition, allowing automated generation of the physicians report. Most of the technologies which will support this integration are being developed outside

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the medical world. It is these types of technologies which drive multimedia applications, meaning digitized material, either real-time or stored, comprising more than one medium: text, voice, video, images, graphics etc. Examples include network technologies for high data rates, data base techniques, voice recognition techniques, (lossy) data compression and others. Such technologies will help to create and process computerized patient files. It is obvious that much effort has been put into standardization to allow the communication between modality equipment, review stations, archiving systems and RIS and HIS systems. DICOM has become that standard. These are only a few examples of supporting technologies which facilitate the eventual complete integration of information flow in the hospital. As stated at the beginning of this article, the intelligent use of hospital data will lead to better and more cost effective health care. Conclusion A wide range of imaging technologies is required to optimally visualize as much of the wide diversity of anatomical structures, and physiological and pathological processes, as possible. Many imaging technologies (image intensifiers, ultrasound, computed tomography, magnetic resonance) have found wide medical acceptance in the last four decades. The speed of innovation in these modalities remains high. Others imaging techniques, such as positron emission tomography, remain in niche environments. The primary reason for success is a modalitys ability to supply new clinical information which is useful for the routine care of large numbers of patients. The demand for more effective and less invasive therapy increases the need for real-time imaging. The choice of an imaging modality for a given procedure is determined by its ability to display both the patients anatomy and the operators instruments. Patient access and the safety of both patient and operator are also of major concern. Multi-modality imaging can often enhance medical decisions. At present, this is most commonly done by separately viewing several examinations, and merging results in the physicians head. Combining images in a workstation can facilitate this process to the benefit of the radiologist, referring physician and, ultimately, the patient. The total amount of available information describing an individual patient continues to increase. Information systems facilitate access

to images, reports, laboratory values etc. Increased efficiency of information access might simultaneously reduce costs and, more importantly, improve the quality of health care. Managing the efficient use of available medical resources is essential. Medical imaging and medical information management are two of the key technologies which are indispensable parts of the solution.
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8. CD-Medical: storage and review station for cardiac cine images.

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