Medical Imaging Rob Ireland Thank you very much for inviting me here tonight. I’m very grateful to Action Research for the encouragement and support over the two years of my Research Training Fellowship. The aim of the next half hour or so is to give you an introduction to medical imaging of the brain. I'm sure that everyone in this room appreciates the importance of medical imaging or scanning. We’ve all had a medical scan of some sort, even if it’s just an X-ray, and brain imaging, in particular, plays a vitally important clinical role. Rob Ireland

Medical Imaging Anatomy Structure Physiology Function X-ray CT MRI So, why do we want to image the brain? Well, the simple answer is that it gives useful clinical information about what the brain looks like - the anatomy of the brain - and how the brain is working or functioning. We often need both anatomical and functional information because, for example, the parts of the brain may look normal but may not necessarily be working normally. This information is used in the diagnosis, management and research of a wide range of different disorders. Anatomical imaging is performed using techniques called x-ray CT and MRI, while functional imaging can be conducted using methods called SPECT and PET. It’s these four imaging techniques that I’m briefly going to introduce in this evenings talk. X-ray CT MRI SPECT PET Complimentary clinical information for diagnosis, management and research

X-rays: history Röntgen 1895 8 Nov discovery of x-rays 22 Dec image of wife’s hand 13 Jan first medical use During an extraordinary couple of months of intense investigation, Röntgen discovered x-rays on 8 November 1895, produced the first bone images from his wife's hand on 22 December. Medical applications of two-dimensional x-ray images swiftly followed. Amazingly, the first medical use was reported on 13 January 1986 in Birmingham, UK.

X-rays: history 1896 Advertisement The use of x-rays spread extremely quickly as Röntgen had no interest in patenting any aspect of the discovery. This is an early advert for x-ray equipment from 1896. You can see that marketing strategies haven’t changed much - they were already claiming a new and improved x-ray tube!

X-rays (2D) Conventional x-ray 2D (planar) no perception of depth Of course x-rays are still used in great numbers today for standard examinations. However, when a more detailed images is required, the problem with conventional x-rays is that they only provide a 2D image of a 3D person - there’s no perception of depth.

X-ray CT (3D) Computed Tomography (CT) tomos (cut or slice) over 60 years after the discovery of x-rays “We cannot imagine a market for an apparatus that makes radiographic cross-sections of the head.” A major x-ray manufacturer, June 1960 What is required is a 3D image. We call this tomographic imaging, which is the process of isolating a section of an organ from the overlying structures. From the Greek tomos, a cut, and graph, written. Although X-rays have obviously been immensely useful in medicine, it took over sixty years before x-ray tomography solved the problem of lack of depth perception. The delay was partly due to x-ray manufacturer’s not being able to perceive benefits from a 3D system. They also couldn’t believe that hospitals would be willing to pay for such potentially expensive pieces of equipment. For example, one researcher (Oldendorf) was told “even if it could be made to work as you suggest, we cannot imagine a significant market for such an expensive apparatus which would do nothing but make radiographic cross-sections of the head” by a major x-ray manufacturer in June, 1960.

Tomographic Imaging By doing this, we can get images from any slice of the body. (Video clip from the Virtual Human Project, modified by Rob Ireland.)

X-ray CT (3D) Godfrey Hounsfield (EMI Ltd) 1971 first CT in Atkinson Morley (Wimbledon) "This work is epoch-making in medical radiology. No other method has led to such remarkable advances as computed tomography.” Nobel Prize 1979 Flush with the profits from The Beatles records, EMI employed Godfrey Hounsfield to develop a system for tomographic imaging who filed a patent for x-ray CT in 1968. Hounsfield installed the first practical CT scanner at the Atkinson Morley Hospital in Wimbledon in 1971. In contrast to the early scepticism shown in the early 1960s, the Nobel Institute was rather more enthused by Cormack and Hounsfield's work in their press release for the 1979 Nobel Prize in Physiology or Medicine: "This work [is] epoch-making in medical radiology. No other method within X-ray diagnostics has, during such a short period of time, led to such remarkable advances, with regard to research and number of applications, as computer-assisted tomography."

X-ray CT: how it works Images from a number of directions Use a computer to reconstruct images

X-ray CT: modern scanners Royal Hallamshire Hospital, Sheffield

X-ray CT: modern scanners Royal Hallamshire Hospital Sheffield

MRI Anatomy Function Structure Physiology X-ray CT MRI SPECT PET

MRI - history Magnetic Resonance Imaging (MRI) 1924 Pauli fundamental theory (proton spin) 1946 Bloch & Purcell measurement technique “This discovery won't revolutionise industry or help the housewife.” Boston Herald, following the award of the 1952 Nobel Prize The development of X-ray CT paved the way for research and development into other tomographic medical imaging devices, in particular MRI. The development of MRI is a lesson in how valuable fundamental research can be. The theoretical basis for MRI was set out by Pauli in 1924 who established the idea of proton spin.Methods of measuring the phenomena were developed independently by the Nobel Prize winners Bloch and Purcell in 1946.

21 years later … potential medical applications MRI - history 21 years later … potential medical applications 1973 Lauterbur spatial localisation of signals To get images, it’s not enough to just have a set of measurements. You need to know which part of the body the measurements relate to. Less than a quarter of a century later, investigators of medical applications of (these techniques) [NMR] were encouraged by the commercial success of x-ray CT, which demonstrated the willingness of hospitals to invest in extremely expensive imaging equipment. In 1973, the spatial localisation of the NMR signal by the imposition of a magnetic field gradient was proposed by Mansfield & Grannel and independently in Nature by Paul Lauterbur, who displayed the first MR image.

MRI - history 1977 first thoracic image However, the first thoracic images were published in 1977 by the more commercially-minded Raymond Damadian, who had previously patented an "Apparatus and method for detecting cancer tissue" having claimed to have conceived the idea of a whole body scanner.

Royal Hallamshire Hospital, Sheffield MRI - modern scanners Royal Hallamshire Hospital, Sheffield First, anatomical imaging. One method of imaging the anatomy is to use magnetic resonance imaging. Many people have found MRI to be quite claustrophobic. The latest design of MR systems are more open (movie).

MRI - modern scanners MRI provides finely detailed images of the brain’s structure. These three images show three different slice orientations for a normal subject.

Comparison of MRI and CT Gross Anatomy MRI CT

Functional Imaging Anatomy Function Structure Physiology X-ray CT MRI So that’s anatomical imaging. Next, let’s take a look a functional imaging. I’ll treat PET and SPECT together as they’re quite similar techniques. X-ray CT MRI SPECT PET

Functional Imaging Angelo Mosso 1848-1910 Mental activity Normal 12 o’clock What do we mean by functional imaging? The idea of monitoring how the brain works comes from some work conducted late last century by an Italian called Angelo Mosso. Mosso noticed that in newborn babies, before the skull is fully developed, you can see small pulses in the head. He decided to investigate this phenomenon in adults who had suffered damaged skulls. This was his apparatus for measuring the pulses of pressure changes. The story goes, that he had this set up on a subject one day when the 12 o'clock bells started to ring from the local church // and his pressure measurements changed dramatically. What Mosso realised was that the bells had reminded the subject to say his midday prayers to himself. Now, the pulses represented blood flow in the brain, and this was the first time that it was realised that mental activity leads to an increase in blood flow. Mental activity Increased blood flow

PET - history 1953 Massachusetts General Hospital It’s this flow of blood in the brain that enables brain function to be imaged. In the 1950s, people started to investigate functional imaging. This photo show one of the first human experiments using a technique called PET. The resulting image shows an increase in the blood flow.

Chemical emits two signals PET - how it works Chemical emits two signals detectors With PET, a small amount of a chemical that binds to the blood is injected into the body and emits signals from areas of the brain in which blood is flowing. These signals are detected and used to form an image of blood flow in the brain. PET is an accurate technique two signals in opposite directions are produced. This makes it easier to know where in the brain the signals originated.

SPECT - how it works Chemical emits single signal Camera records signals around the head Chemical emits single signal SPECT is a related functional imaging technique. This time though there is only one signal, which means that the method is less accurate than PET. However, SPECT is much more common than PET because it is less expensive and more practical procedure. less accurate than PET less expensive

Royal Hallamshire Hospital Sheffield SPECT - modern camera Royal Hallamshire Hospital Sheffield This is what a typical SPECT camera looks like - quite different from the CT and MRI systems.

Comparison of MRI and SPECT Comparing anatomical and functional images, it’s obvious there’s a big difference between the two. On the left, the MRI image shows fine details, while on the right, we’ve got a fuzzy functional image. Although, there’s quite a big difference between the two, I think you can appreciate there is some form of relationship between the two. It’s this relationship that I’ve been examining in my research. MRI SPECT

Ultrasound 6 months later