Revolutionising The Understanding And Performance Of Clinical MRI

If you have ever had an MRI scan, you will have come into contact with work by Kiwi medical imaging pioneer Graeme Bydder. Much of the content of present-day clinical MR examinations is derived from his early work. At age 78, Mātai Scientific Advisory Board Member and Emeritus Professor at the University of California San Diego (UCSD) Bydder is still a major influencer in imaging advancements.

A new journal paper headed by Professor Bydder, involving the Mātai team, has recently been published in the journal Quantitative Imaging in Medicine and Surgery, which changes the way clinicians think about MR image contrast and has the potential to transform the way neuro-inflammatory diseases of the brain and other conditions are imaged.

The paper, titled 'Improving the Understanding and Performance of Clinical MRI using Tissue Property Filters (TP-filters) and the Central Contrast Theorem, MASDIR (Multiplied, Added, Subtracted and/or Divided Inversion Recovery) Pulse Sequences and Synergistic Contrast MRI (scMRI)' provides a mathematical framework for increasing the sensitivity of MRI to subtle signs of disease. The concepts in the paper evolved from work by Professor Graeme Bydder and Professor Ian Young, both pioneers in the development of clinical MRI. Mātai Clinical Lead Dr Daniel Cornfeld and Mātai MRI Charge Technologist Paul Condron, contributed to the work by applying and refining many of the concepts in the manuscript and producing proof-of-concept images based on the new framework.

Dr Daniel Cornfeld said “It is hoped that this new framework will make it easier for physicians to understand what they are seeing on images. This is important because many of the concepts historically taught to radiologists and scientists about why things look the way they do are misleading and in some cases incorrect. Better understanding of why the images look the way they do also makes it easier to develop new and improved image types for detecting disease.”

The mathematical framework explains the dark/light image contrast seen on the images, and makes it possible to design sequences that will detect very subtle abnormalities. While there are always new MRI techniques being described in the literature, most depend on state-of-the-art hardware and software only available at top research institutions. The concepts in this paper can be applied to images that can be obtained on regular clinical scanners.

The new techniques, called MASDIR pulse sequences, which Multiply, Add, Subtract and/or Divide existing Inversion Recovery clinical images acquired with certain settings input by the user, improve tissue contrast by 5-15 times compared to current “gold standard” techniques. This makes subtle changes due to disease far easier to see. These techniques dramatically improve the visualisation of subtle disease in Multiple Sclerosis, the archetypal neuroinflammatory disease of the brain.

There is increasing evidence that neuroinflammation is a major contributor to a wide range of diseases in the nervous system besides Mulitple Sclerosis including traumatic brain injury, Myalgic Encephalitis/Chronic Fatigue Syndrome, long COVID, Alzheimer's disease and Parkinson's disease. These diseases are also likely to show much more abnormality with the new techniques. It is also hoped that the techniques will be useful in other parts of the body. For example, Mātai plans to see if MASDIR techniques can increase the sensitivity of MRI to prostate cancer.

A standard MRI of Multiple Sclerosis is shown in Figure 1A, which appears normal, but the MASDIR sequence in the matched slice (Figure 1B) shows a large white matter plaque in the brain stem.

Notes

Amplifying the contrast of Magnetic Resonance Images to reveal unrecognised disease of the brain

(i) The main advantage of MRI is that it often shows soft tissue contrast of this type better than any other imaging technique, and this is what is exploited in MRI of the brain. While large tumours often change the gross anatomy of the brain, more subtle diseases frequently do not change anatomical boundaries but show image contrast i.e. a difference in voxel brightness or signal, typically between normal and abnormal tissue.

(ii) To produce contrast different MRI pulse sequences are used. They exploit differences in the MR properties of tissues such as the time constants T1 and T2 which describe return of nuclear magnetisation to equilibrium after it is perturbed. T1 and T2 are very sensitive to the local physical and chemical environment and are frequently prolonged in disease including those in which there is increased water present.

(iii) The first disease to benefit from the high contrast of MRI was Multiple Sclerosis (MS) where in 1981, 112 lesions were seen in ten patents with MRI compared to 19 lesions with Xray CT. MS has since become the archetypal disease for demonstrating the clinical value of MRI.

(iv) The basic pattern of pulse sequences used in clinical MRI depends mainly on T1 and T2, and has not changed since the early days of MRI 30-40 years ago, although the contrast with which lesions are seen with on T1 and T2 pulse sequences has increased about five times due to engineering improvements to MRI systems during this time.

(v) The new technique Multiplies, Adds, Subtracts and/or Divides existing Inversion Recovery pulse sequences (hence the name MASDIR). It improves contrast 5-15 times compared with conventional state of the art Inversion Recovery sequences and so accomplishes more in one dramatic move than was previously achieved over three or four decades. This 5-15 times increase in contrast is in addition to that produced by the 30-40 years of improvements in engineering.

The advantages of MASDIR sequences are seen in a case of MS shown in Figure 1A where the state-of-the-art conventional FLAIR MRI pulse sequence shows no abnormality, but the MASDIR sequence in the matched slice (figure 1B) shows a lesion in the brain stem.

(vi) In addition to being the archetypal disease for MRI, MS is a classic example of a neuroinflammatory disease. There is increasing evidence that neuroinflammation is a central pathological component in a wide variety of other diseases of the nervous system besides MS including Alzheimer's disease, Parkinson's disease and chronic traumatic encephalopathy.

(vii) Of particular interest in this context are Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and long-COVID where neuroinflammation is thought to be particularly prominent, but conventional state of the art MRI scans are usually negative. As with MS, amplifying the contrast 5-15 times with MASDIR sequences may reveal abnormalities in the brain in these diseases which have previously not been detectable.

(viii) Understanding the contrast produced by MASDIR sequences is greatly helped by mathematical modelling and Dan Cornfeld, consultant radiologist, has developed an interactive series of Apps which explain the sequences in detail. It is very difficult to interpret MASDIR images without mathematical modelling of this type.

The modelling is shown in Figure 2 which compares the contrast produced by a conventional Inversion Recovery sequence (vertical pink arrow on the right) to the contrast produced by a MASDIR sequence (blue arrow on the right). There is five times as much contrast produced by the MASDIR sequence for the same change in T1.

(ix) The new technique needs precise targeting at the transition between different tissues, and this has been achieved by Paul Condron, charge technologist using an advanced MRI system installed at the Matai Medical Research Institute in Tairāwhiti-Gisborne.

Dr. Graeme Bydder, Emeritus professor, Radiology, University of San Diego California (UCSD), USA. Mātai Scientific Advisory Board.

Professor Bydder is a pioneer of new MRI methods. He is a graduate of the Otago Medical School and is currently an emeritus professor of radiology at the University of California, San Diego. He worked on the world’s first commercial whole-body CT machine (the EMI CT5000/5) at Northwick Park Hospital in London from 1978-80, and the world’s first commercial cryomagnet based MRI system (1981-1990) at Hammersmith Hospital in London. Graeme has published over 300 peer-reviewed journal articles on MRI techniques, clinical applications of MRI, image interpretation and related subjects, and has over 26,000 citations. Much of the content of present-day clinical MR examinations is derived from his early work.

DR DANIEL CORNFELD, MĀTAI CLINICAL LEAD

MD, FRANZCR

Mātai Clinical Lead and Honorary Senior Lecturer at the University of Auckland

Daniel Cornfeld is also the Head of Department for Radiology at Hauora Tairāwhiti (Gisborne Hospital and holds a degree in Physics from Princeton University. Previously, Dr Cornfeld was the Chief of Abdominal MRI and Associate Professor of Radiology at Yale University. He enjoys applying and evaluating new imaging tools, and has significant clinical and research experience in experimental design using state-of-the-art imaging technologies.

PAUL CONDRON, MĀTAI CHARGE TECHNOLOGIST

BSC (HONS) DIAGNOSTIC RADIOGRAPHY, PG CERT (CI), PG DIP MRI

Paul Condron is responsible for the MRI operations. He comes to Mātai with a wealth of knowledge and experience in both clinical imaging and research. His research experience includes cardio-vascular and neurological imaging, in particular acute stroke, Alzheimer’s, working-age Dementia, and Neonatal head injuries.

DR SAMANTHA HOLDSWORTH

BSC(HONS), MSC, PHD

Matai Director & Associate Professor (University of Auckland), Principal Investigator Center for Brain Research

Dr Holdsworth is a medical physicist with 22 years of experience in new and advanced MRI methods. She is a pioneer of super-fast, high resolution MRI methods and amplified MRI (a new method of visualising brain motion). Formerly, as a Senior Researcher at Stanford University, she successfully translated a variety of her MRI methodologies to clinical practice. Her methodologies led to improved detection and diagnosis of brain disorders and disease. She is involved in a number of medical research initiatives, including traumatic brain injury, ADHD, methamphetamine, neurogenerative disease, and idiopathic intracranial hypertension.

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