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7T MRI in cerebral small vessel disease- progress report. 20/11/2014

We have set up the MRI protocol at Oxford and optimised the MR sequences we will be utilising. This includes T1-weighted imaging, T2-weighted imaging, time of flight (ToF) MR angiography and black blood imaging. The project is now progressing well. We have scanned two normal volunteer and 3 patients with cerebral small vessel disease (SVD) so far. 2 further patients are due to be scanned later this month. We had a meeting on 13/11/14 at the FMRIB in Oxford to discuss the imaging carried out so far. Everyone involved in the project attended the meeting including Prof Hugh Markus, Prof Peter Jezzard, Prof Peter Rothwell, Dr Andrew Mackinnon and Ms Olivia Veissmann. At the meeting we reviewed all the imaging we had carried out on the 7T scanner. This is discussed below.

MR angiography : We are using high resolution (0.31mm) Time of Flight (ToF) imaging. We have showed that 7T MRI allows non-invasive imaging of the cerebral perforating arteries in SVD, i.e. the pathological arteries themselves (Figure 1). We also compared ToF MRA at 3T and 7T and showed that 7T imaging was able to depict the lenticulostriate branches of the middle cerebral artery in much greater anatomical detail than 3T MRI (Figure 2).

Vessel wall imaging : The angiographic technique above depicts the lumen of the vessel and can therefore only detect luminal narrowing when it is relatively severe. We have shown that it is able to obtain black blood imaging in order to visualise the vessel wall itself which may allow the detection of atheroma and other vessel wall pathology before luminal narrowing becomes apparent.

Cerebral Microinfarcts : In order to visualise microinfarcts we are obtaining high resolution (0.8mm) T1-weighted imaging and T2-weighted imaging.

Publications : Benjamin P, Viessmann O, MacKinnon A, Jezzard P, Markus H. 7 Tesla MRI in Cerebral Small Vessel Disease. Accepted in International Journal of Stroke. This is a review article which discusses the opportunities and challenges of 7Tesla MRI in SVD. We have used our own images in this article.

Grants : We aim to submit a grant application to the BHF in February 2015 for further imaging of patients with SVD.

7T MRI offers a number of novel insights into the arterial and parenchymal lesions associated with SVD. The ability to visualise the perforating arteries will allow the role of atherosclerosis and focal stenosis in disease pathogenesis to be explored. The ability to visualise CMIs will allow their role in SVD including their contribution to brain atrophy to be determined.

Figure 1: Arterial imaging using 7T MRI in a patient with SVD

7T ToF MRA (resolution = 0.31 mm isotropic) of highly tortuous lenticulostriate arteries (red arrow) seen in a patient with confluent white matter hyperintensities and several lacunar infarcts. Image is displayed in radiological convention.



Figure 2: Arterial imaging using 7T MRI.

A) 3D reconstruction of a 3T ToF MRA maximum intensity projection (resolution = 0.4 mm isotropic) of large lenticulostriate arteries originating from the middle cerebral arteries on the right and left in a normal volunteer. B) 3D reconstruction of a 7T MRA image obtained from the same subject (resolution = 0.31 mm isotropic). Images are displayed in radiological convention.







Traumatic spinal cord injury (TSCI) is a devastating condition. Most patients are young men and about a third remain paralysed or wheelchair bound. In the USA, the annual cost of caring for TSCI patients was estimated at $19 billion in 2011.

There is a lack of monitoring techniques in the neurointensive care unit (NICU) to guide management of patients with acute severe TSCI. As a result, the optimum mean arterial pressure (MAP) is unknown as is the role of bony decompression (laminectomy) [1]. The ability to monitor fundamental physiological variables from the site of injury such as intraspinal pressure (ISP) and spinal cord perfusion pressure (SCPP = MAP minus ISP), would be a major advance by allowing doctors to limit secondary spinal cord damage that arises from hypoperfusion.

Prof. Papadopoulos’ group recently reported a novel method to monitor ISP and SCPP at the injury site in TSCI patients in NICU [2]. The procedure involves inserting a pressure sensor intradurally between the swollen spinal cord and the dura. The data show that, after severe TSCI, ISP is high (typically 20 – 40 mmHg) and SCPP low (typically 40 – 60 mmHg). By intervening to increase SCPP, outcome in some patients was improved, as assessed using motor evoked potentials and a limb motor score. Mannitol administration, reduction in paCO2, and increase in sevoflurane dose had little effect on ISP after TSCI, even though these manoeuvres have a major effect on intracranial pressure (ICP) in traumatic brain injury (TBI). Increasing the dose of inotropes caused an increase in ISP and MAP, but with a net increase in SCPP.

Prof. Papadopoulos’ group proposed a novel way to optimise SCPP in patients with TSCI [2]. They defined the parameter sPRx, which stands for spinal Pressure Reactivity index, and is the running correlation coefficient between ISP and MAP. sPRx ≤ 0 denotes intact pressure reactivity, whereas PRx > 0 indicates impaired reactivity. A plot of PRx vs. SCPP yields a U-shaped relationship. The optimum SCPP (termed SCPPopt) corresponds to the minimum sPRx. Reducing the SCPP below SCPPopt, causes hypoperfusion of the cord and is detrimental. Hyperperfusing the injured cord is also detrimental. An interesting observation is that SCPPopt varies widely between TSCI patients. This suggests that general guidelines (eg. aiming for MAP between 85 – 90 mmHg) may be meaningless.

There are other interesting findings with important clinical implications. One finding is that bony ‘decompression’ (laminectomy) does not adequately decompress the injured cord, which remains compressed against the surrounding dura. This may explain why studies of bony ‘decompression’ without dural opening have not convincingly shown a beneficial effect on outcome. Prof. Papadopoulos suggests that a laminectomy without expansion duroplasty in TSCI is analogous to a decompressive craniectomy without durotomy for TBI, which is largely ineffective at reducing ICP. Another interesting finding is that laminectomy allows compression forces applied to wound to be transmitted to the spinal cord, thus reducing SCPP and potentially causing further damage. This observation has important implications for nursing care. It raises the possibility that a TSCI patient who is nursed supine with a pillow under the wound may develop spinal cord ischaemia from wound compression.

Though ICP monitoring to guide management of patients with TBI is the standard of care, ISP monitoring to guide management of patients with TSCI is not used. ISP monitoring is a novel idea based on basic physiological principles and may be applied to any spinal cord pathology that causes spinal cord swelling e.g. oedematous transverse myelitis.

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1.        Werndle MC, Zoumprouli A, Sedgwick P, Papadopoulos MC. Variability in the treatment of acute spinal cord injury in the United Kingdom: results of a national survey. J Neurotrauma. 2012;29:880-8.

2.        Werndle MC, Saadoun S, Phang I, Czosnyka M, Varsos GV, Czosnyka ZH, Smielewski P, Jamous A, Bell BA, Zoumprouli A, Papadopoulos MC. Monitoring of spinal cord perfusion pressure in acute spinal cord injury: initial findings of the injured spinal cord pressure evaluation study. Crit Care Med. 2014;42:646-55. Editorial: Crit Care Med. 2014;42:749-50.




 A histological study of VEGFR2 in the aging human brain


Dr Atticus Hainsworth
Cardiovascular Medicine, St George’s University of Medicine

Arteries can contract or dilate. This is what controls the supply of blood to downstream tissues, which is especially important in brain arteries, where blood supply is matched to the level of brain activity in particular brain areas. Insufficient blood supply to a brain region causes severe symptoms, seen most dramatically in a “stroke”, or brain attack. Thus, effective control of blood flow in brain arteries is crucial, and this is the job of small muscle cells in the artery wall, called myocytes.

No-one knows the lifespan of a brain artery myocyte – it may be ten years or more. We presume that they are replaced, but we don’t know how frequently. In our laboratory, we study myocytes in post mortem human brains that were donated for research. These brains are stored in brain banks and they give us a unique opportunity to study human disease.

Recently we were very excited to discover a receptor molecule called VEGFR2 in the myocytes of these brain specimens. VEGFR2 is the receptor for vascular endothelial growth factor, an important protein that controls growth of new blood vessels. With the help of the Neuroscience Research Foundation, we have confirmed that this finding is universal in aged human brains. We presented our findings at the annual European Stroke Conference in Hamburg in May 2011.

We are now exploring the actions of this receptor in myocytes. Based on insights from this study, we aim to control myoctes in brains of aged human subjects. This would allow us to prevent brain vascular diseases such as stroke and vascular dementia.


Figure showing a small artery from human brain labeled with VEGFR2 (red) and a myocyte protein (SMA, green). Cell nuclei are labeled blue.


Investigation of the molecular causes of inherited forms of motor neurone degenerative disease
Professor Andrew Crossby
Basic Medical Sciences, St George’s University of London



The motor neurone diseases (MND) are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including walking and movement, talking, breathing, and swallowing. Although in most cases MND appears for no apparent reason there are a small proportion of inpiduals who have a family history of the disease (called familial MND) indicating that inherited genetic mistakes may cause the condition. As well as classical MND there are many different inherited neurological conditions which also involve the degeneration of motor neurones, and recent research suggests that the cellular problems that cause many of these conditions may in fact be related. Identifying the genes that cause various forms of these conditions is therefore important because it provides important clues as to how motor neurones function normally and how they may be damaged in MND.

There are two aspects to our research into MND funded by the Neuroscience Research Foundation. Firstly we aim to discover new genes that cause inherited familial forms of MND and related disorders to add to our growing knowledge of the genetic causes of motor neurone degeneration. Secondly we aim to study the function of these molecules in more detail to identify which biological pathways may be common to different forms of motor neurone degenerative disease. These results will hopefully provide information which is crucially important for the ultimate development of a treatment for these diseases. clip_image003.jpg

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