Ian Robert Young OBE and the development of MRI

Ian Robert Young OBE PhD DSc (Hon) FRS FREng FIEE FlnstP FRCR (Hon) FRCP (Hon) (11 January 1932 – 27 September 2019)

Ian Young was born in London on 11 January 1932, the eldest of three sons. His father, John Stirling Young, was Regius Professor of Pathology at the University of Aberdeen from 1937 to 1962. Ian was educated at Sedbergh School in Cumbria, North West England and studied natural philosophy at the University of Aberdeen. He completed his BSc in 1954, and his PhD in Optical Metrology at the University under the supervision of Professor Reginald V Jones FRS (1911-1997), who was famous for many feats of scientific intelligence and the development of electronic countermeasures during World War II.

EMI, Computed Tomography (CT)
Ian joined the Electric and Musical Industries (EMI) Central Research Laboratory (CRL), Hayes, Middlesex in August 1976. The company specialised in entertainment and defence until quite unexpectedly, and at very little cost to the company, Sir Godfrey Hounsfield FRS developed the world’s first head CT scanner which was first used in 1971. This transformed neuroradiology. In 1975 he followed this with the CT5000 whole body scanner which had wide application in oncology, as well as chest and musculoskeletal disease. CT was a major departure for the company which had no significant track record in X-ray technology or medical equipment. Following the invention of MRI by Paul Lauterbur in 1973, EMI decided to expand its role in medical imaging and established a Nuclear Magnetic Resonance (NMR) group.

0.1T Walker MRI System at the EMI CRL
The NMR group began with a Walker 0.1T resistive magnet (Fig. 2) and, under the direction of Hugh Clow and Ian Young, produced the world’s first published human MR image of the brain in November 1978. This was followed by an inversion recovery (IR) image of Ian Young’s brain in Autumn 1979 which showed very high grey-white matter contrast (Fig. 3B). The image was shown by Godfrey Hounsfield during his Nobel prize lecture on Computed Medical Imaging on 8 December 1979 (1) together with his diagram explaining the T1 dependent contrast (Fig. 3A). On the curve close to the numeral 2 white matter has a higher signal than grey matter (Fig. 3A) which is what is seen on the image (Fig. 3B).

The Cryogenic System, Neptune
With funding from the Scientific and Technical Services Branch of the Department of Health and Social Security headed by Gordon Higson (2), Ian’s group next built a 0.15T system based on the world’s first commercial large bore cryomagnet (Fig. 4). This was constructed by Oxford Instruments headed by Sir Martin Wood FRS. The MR system was shifted to Hammersmith Hospital, London in January 1981, and patient imaging began there in March 1981. Unlike the Walker system which looked like a laboratory prototype, the cryomagnet based system has the appearance of a modern MRI machine.

Competition with CT
In order to obtain the large scale funding necessary to develop MRI into a clinical product it was essential to show that the new technique could equal or surpass state of the art CT, but this was not an easy task. Brian Worthington FRS from Nottingham said in 1996: “CT had developed rapidly in the period from 1974 to the early 1980s and this was being compared with MRI, an embryonic technique. As a neuroradiologist I was appalled to see that the commonest primary benign tumour in the intracranial compartment, the meningioma, was invisible on MRI. I had struggled to try and separate tumour from oedema which was easily done with contrast in CT, but we were having great difficulty with MRI. By mid-1982 there were some very difficult problems with MRI to be addressed” (3).

In spite of the problems, in November 1981 Ian published a study of 10 Multiple Sclerosis (MS) patients in which 112 lesions were detected with MRI and only 19 were seen with CT (4). It was a quantifiable, decisive clinical advantage for MRI over CT, and led to large scale investment by industry in MRI research and development. Oxford Instruments’ order book for magnets increased from £1M in 1981, to £25M in 1982.

The success with the IR sequence was followed by David Bailes’ development of the heavily T2-weighted SE sequence (5) in which abnormalities in the brain were highlighted as part of a Multi Sequence Approach to the diagnosis of disease with MRI.

In addition, use of Spin-warp data acquisition developed by Jim Hutchison and Bill Edelstein from Aberdeen allowed imaging in the sagittal plane and provided iconic images of the brain with white matter appearing white, grey matter appearing grey and CSF appearing black, corresponding to the post-mortem appearance of the brain (Fig. 5). Images of this type were unattainable with CT.

The “Field Wars”
However, the MR imaging world was turned on its head at the November 1982 meeting of the RSNA when General Electric (GE) showed high quality brain images obtained at 1.5T, ten times the field strength of 0.15T that Ian and others were operating at. The GE 1.5T system was aggressively marketed even though the company had no product to sell. Customers were strongly advised not to buy other companies’ lower field systems, but instead to buy the 1.5T GE product as soon as it became available.

This was the beginning of the “field wars” which dominated MRI for the next 4-5 years. Ian and his group persisted at 0.15T, developed about 30 new receiver coils (e.g. Fig. 6), used low bandwidth acquisitions, performed phase sensitive flow imaging and implemented the short inversion time IR (STIR) pulse sequence which suppressed fat signals and produced very high contrast images of abnormalities, as well as susceptibility weighted imaging (SWI) in 1987.

There were problems at high field: images were degraded by artefacts from susceptibility, chemical shift and motion much more than they were at low field. Over time Ian and his group showed that the field argument was not a cut and dried matter; it was possible to perform clinically competitive studies at low field using much cheaper systems than 1.5T ones.

Contrast Agents, Gadolinium-DTPA
Ian’s group also used the contrast agent Gadolinium-DTPA developed by Hanns-Joachim Weinmann of Schering and performed the first clinical study with this agent (6) as well as many subsequent studies including ones on meningiomas which were well demonstrated (7). The agent showed enhancement that was equal or superior to CT and allowed comprehensive MRI examinations of the brain for the first time. It also had wide application in body MRI including oncology.

Endocavity and Interventional MRI
These approaches were developed by Nandita deSouza and David Gilderdale of Ian’s group who made internal anal, rectal, cervical, vaginal and prostate coils including paediatric adaptations. They showed a level of anatomical resolution and sensitivity to disease that was not achievable with external coils. This was extended to endoscopy and image guided biopsy. Nandita also developed thermal ablation in different forms for disease of the prostate and continued her work at the Institute of Cancer Research, London.

FLAIR, later T2-FLAIR
The Fluid Attenuated IR (FLAIR) sequence was developed by Jo Hagnal who used an inversion pulse to null CSF and doubled the TE of T2-weighted SE sequences to provide unambiguous high contrast visualisation of abnormalities in a wide range of disease of the brain including MS (Fig. 7). The sequence attained very wide acceptance for clinical brain studies.

The Neonatal System
After establishing the first MRI study of children in 1982 and supporting a very active paediatric MRI group centred around Lilly Dubowitz for over a decade, Alasdair Hall constructed a dedicated neonatal system using a very short bore (35 cm), self-shielded 1.0T magnet built by Oxford Magnet Technology (OMT). It was installed in the Neonatal Intensive Therapy Unit (NITU) at Hammersmith Hospital in 1995 and allowed examination of very premature and very sick infants without requiring transport out of the NITU. These patients had previously not been examinable with MRI because of the risks in taking them elsewhere and providing the necessary monitoring and intensive care. Infants down to 24-25 weeks Gestational Age were examined, often repeatedly, and details of normal development and disease were established. This work has been continued by David Edwards at Kings College, London.

The History of the Development of MRI and MRS in the UK (MRIS History UK)
Ian helped establish an eBook to include historical accounts by authors from different disciplines and institutions within the UK. The contributions would be proof-read, critically edited and peer-reviewed. Ian wrote the first article for the eBook which went through multiple revisions before it was accepted by the reviewers (8). The eBook is being continued by Martyn Paley (9) and Graeme Bydder (10).

Final work
Ian extended the IR sequence beyond the double IR (DIR) sequence described in 1985 to combine two or more IR images in the Multiplied, Added, Subtracted and/or fiTting (MASTIR) sequence. An example of this is subtraction of two IR images with different TIs together with a further IR pulse multiplication to suppress fluid resulting in the Multiplied Subtracted IR (MSIR) sequence. It shows far more extensive abnormality in the central white matter of the brain in a case of MS than a conventional heavily T2-weighted SE sequence (Fig. 8).

Conclusion
Ian’s group was the first to demonstrate a decisive clinical advantage for MRI over state of the art CT. This was critical in facilitating the investment in research and development necessary to produce a clinical product.

His group pioneered clinico-industrial collaborations which became the preferred mode of development for MRI. This was strongly supported by Surya Mohapatra of Picker/GEC. Those who did not establish arrangements of this type often lagged behind in the clinical arena.

Ian’s approach to MRI which exploited high soft tissue contrast and the many different MR tissue properties remains the basic approach to clinical MRI today.

Before MR contrast agents became available Ian’s group found important clinical applications such as MS and posterior fossa disease (after meningiomas had been excluded with contrast enhanced CT). When these agents did become available for clinical MRI use in 1984 they were the first group to describe their application.

An understanding of what clinicians wanted to see led to the development of the Multi Sequence Approach producing in the brain one class of images that looked like classic anatomical sections as well as a second class of heavily T2-weighted SE, and FLAIR (later T2-FLAIR) sequences which highlighted abnormalities.

After beginning clinical work in 1981, by 1985 Ian and his group had published five of the ten most cited papers on clinical MRI. Two of the others were from the University of California, San Francisco (UCSF) with one each from the Mallinckrodt Institute of Radiology in St Louis, Case Western Reserve in Cleveland and the Huntington Research Institute in Pasadena.

Ian’s group sustained low field imaging and kept it competitive with a series of technical advances. They employed fat suppression using STIR at a time when chemical shift techniques were unreliable due to eddy current effects. Low field imaging was taken up in Japan (which has over 50 MRI machines per million population compared to about seven in the UK) and is being rediscovered in the US as well as Europe as “high performance, low field” imaging.

Ian has been described as the Father of Clinical MRI. His group produced the first modern MR scanner (Fig. 4) which was very different from the laboratory prototypes previously used by groups working in MRI (e.g. Fig. 2). His work on purpose designed contoured coils is now a universal feature of MR systems. Much of modern clinical brain and body imaging in adults and children uses pulse sequences, artifact control methods, contrast agents and other techniques first demonstrated by Ian Young and his group. The pulse sequences include the T1-weighted IR, T2-weighted SE, T1 and heavily T2-weighted gradient echo and SWI, as well as STIR and T2-FLAIR.

The disease most associated with MRI is MS, the appearances of which were first described by Ian in 1981 (4). James Prichard, neurologist at Yale said “Ian’s early paper on MRI detection of clinically silent demyelinating lesions in MS was the earliest major and still one of the most important MRI discoveries pertinent to neurology. It showed that what we neurologists had always considered an unpredictable intermittent disease is actually a continuously progressive pathological condition of which only the clinical expression is intermittent. That insight both deepened our understanding of the basic processes at work in the disease and provided a new treatment evaluation metric that greatly sped up treatment research.”

Ian was awarded an OBE in 1986 and elected FREng in 1988, and FRS in 1989. He received the Whittle medal from the Royal Academy of Engineering, and the Clifford Paterson medal from the Royal Society as well as honorary fellowships from the Royal College of Radiologists and the Royal College of Physicians. He was awarded an honorary DSc by Aberdeen University. He received gold medals from the Society for Magnetic Resonance in Medicine (SMRM) and the Society for Magnetic Resonance Imaging (SMRI) as well as the silver medal of the International Society for Magnetic Resonance in Medicine (ISMRM), and is the only person to have been honoured in this way.

Ian is survived by his wife Sylvia, their children Graham, Neil and Fiona, as well as six grandchildren.

References
1. Hounsfield GN. Computed Medical Imaging. Nobel lecture, December 8 1979. J Comput Assist Tomogr 1980;4:665-74.
2. Higson GR. Seeing things more clearly. Br J Radiol 1987;60:1049-57.
3. Worthington BS. Making the Human Body Transparent: The Impact of Nuclear Magnetic Resonance and Magnetic Resonance Imaging. In: Wellcome Witnesses to Twentieth Century Medicine. vol. 2, 1998. Eds: Tansey EM, Christie DA. London: The Trustees of the Wellcome Trust p. 32.
4. Young IR, Hall AS, Pallis CA, Legg NJ, Bydder GM, Steiner RE. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet 1981;2:1063-66.
5. Bailes DR, Young IR, Thomas DJ, Straughan K, Bydder GM, Steiner RE. NMR imaging of the brain using spin-echo sequences. Clin Radiol 1982;33:395-414.
6. Carr DH, Brown J, Bydder GM, et al. Intravenous chelated gadolinium as a contrast agent in NMR imaging of cerebral tumours. Lancet 1984;i:484-86.
7. Bydder GM, Kingsley DP, Brown J, Niendorf HP, Young IR. MR imaging of meningiomas using studies with and without gadolinium-DTPA. J Comput Assist Tomogr 1985;9:690-97. The History of the Development of MRI and MRS in the UK (MRIS History UK)
7. Young IR. My involvement with MRI and MRS at EMI and Hammersmith Hospital.
8. Paley MN. A quick scan of my life with MRI and MRS in industry and academia.
9. Bydder GM. Clinical MRI and MRS at Hammersmith Hospital.

The content on this page is provided by the individuals concerned and does not represent the views or opinions of RAD Magazine.