Ian Craven

Magnetic resonance spectroscopy of the brain

Proton magnetic resonance (MR) spectroscopy of the brain is a non-invasive, in vivo technique that allows investigation into regional chemical environments. Its complementary use with MR imaging sequences provides valuable insights into brain tumour characteristics, progression and response to treatment. Additionally, its sensitivity to brain dysfunction in the presence of apparently normal structural imaging has galvanised interest in its use as a biomarker of neurodegenerative disorders such as Alzheimers disease. Accordingly, its integration into clinical imaging protocols within many neuroscience centres throughout the world is increasing. This growing attention is encouraging but if the potential of MR spectroscopy is to be realised, fundamental questions need to be addressed, such as reproducibility of the technique and the biochemistry that underpins the neurometabolites measured. Failure to resolve these issues will continue to hinder the extent and accuracy of conclusions that can be drawn from its data. In this review we discuss the issues regarding MR spectroscopy in the brain with particular attention paid to its technique. Key examples of current clinical applications are provided and future directions are discussed.

Understanding MRI: basic MR physics for physicians

More frequently hospital clinicians are reviewing images from MR studies of their patients before seeking formal radiological opinion. This practice is driven by a multitude of factors, including an increased demand placed on hospital services, the wide availability of the picture archiving and communication system, time pressures for patient treatment (eg, in the management of acute stroke) and an inherent desire for the clinician to learn. Knowledge of the basic physical principles behind MRI is essential for correct image interpretation. This article, written for the general hospital physician, describes the basic physics of MRI taking into account the machinery, contrast weighting, spin- and gradient-echo techniques and pertinent safety issues. Examples provided are primarily referenced to neuroradiology reflecting the subspecialty for which MR currently has the greatest clinical application.

3.0 T MRI of 2000 consecutive patients with localisation-related epilepsy

OBJECTIVES Clinical guidelines suggest that all patients diagnosed with localised seizures should be investigated with MRI to identify any epileptogenic structural lesions, as these patients may benefit from surgical resection. There is growing impetus to use higher field strength scanners to image such patients, as some evidence suggests that they improve detection rates. We set out to review the detection rate of radiological abnormalities found by imaging patients with localised seizures using a high-resolution 3.0 T epilepsy protocol. METHODS Data were reviewed from 2000 consecutive adult patients with localisation-related epilepsy referred between January 2005 and February 2011, and imaged at 3.0 T using a standard epilepsy protocol. RESULTS An abnormality likely to be related to seizure activity was identified in 403/2000 (20.2%) patients, with mesial temporal sclerosis diagnosed in 211 patients. 313/2000 (15.6%) had lesions potentially amenable to surgery. Abnormalities thought unrelated to seizure activity were found in 324/2000 (16.1%), with 8.9% having evidence of ischaemic disease. CONCLUSIONS Since the introduction of the then National Institute for Clinical Excellence guidelines in 2004, the detection rate of significant pathology using a dedicated 3.0 T epilepsy protocol has not fallen, despite the increased numbers of patients being imaged. This is the largest study of epilepsy imaging at 3.0 T to date and highlights the detection rates of significant pathology in a clinical setting using a high-strength magnet. The prevalence of ischaemic disease in this population is significantly higher than first thought, and may not be incidental, as is often reported.

Magnetic Resonance Imaging Biomarkers in Patients with Progressive Ataxia: Current Status and Future Direction

A diagnostic challenge commonly encountered in neurology is that of an adult patient presenting with ataxia. The differential is vast and clinical assessment alone may not be sufficient due to considerable overlap between different causes of ataxia. Magnetic resonance (MR)-based biomarkers such as voxel-based morphometry, MR spectroscopy, diffusion-weighted and diffusion-tensor imaging and functional MR imaging are gaining great attention for their potential as indicators of disease. A number of studies have reported correlation with clinical severity and underlying pathophysiology, and in some cases, MR imaging has been shown to allow differentiation of conditions causing ataxia. However, despite recent advances, their sensitivity and specificity vary. In addition, questions remain over their validity and reproducibility, especially when applied in routine clinical practice. This article extensively reviews the current literature regarding MR-based biomarkers for the patient with predominantly adult-onset ataxia. Imaging features characteristic of a particular ataxia are provided and features differentiating ataxia groups and subgroups are discussed. Finally, discussion will turn to the feasibility of applying these biomarkers in routine clinical practice.

Recent advances in imaging epilepsy

Around 30 000 people are diagnosed with epilepsy every year in the UK. While many of these respond well to antiepileptic drugs, 20–30% have seizures that are resistant to best medical treatment. For these patients it is important to identify any structural abnormalities responsible for generating seizure activity that may be amenable to surgical resection. There are many imaging modalities available to investigate epilepsy including computed tomography (CT), nuclear medicine and magnetic resonance imaging (MRI). Additional techniques are available in specific circumstances including single positron emission CT, diffusion imaging, MR spectroscopy, perfusion imaging and functional MRI. Clearly with so many options, a targeted approach is required to reach a diagnosis efficiently. In this article, each modality is discussed along with the imaging options for the common causes of focal seizure activity.

Autologous hematopoietic stem cell transplantation following pulsed cyclophosphamide in a severely disabled patient with malignant multiple sclerosis

Multiple sclerosis (MS) may run a rapidly progressive monophasic course (the Marburg, or malignant form), that carries a poor prognosis [1]. Autologous hematopoietic stem cell transplant (AHSCT), initially utilised in chronic MS [2], is now occasionally administered in acute aggressive relapsing–remitting MS (RRMS) [3]. We describe a case of malignant-type MS treated with pulsed cyclophosphamide (CY) and non-myeloablative AHSCT. A 21-year-old woman, presented with sensorimotor disturbance to all four limbs in April 2011. Neuro-imaging demonstrated demyelination with enhancement (Fig. 1a), cerebrospinal fluid (CSF) demonstrated 47 lymphocytes and was positive for oligoclonal bands. Serum was negative for aquporin4 (Aq4) antibodies. Three days of 1 g IV methylprednisolone (IVMP) failed to slow progression. A second course of IVMP 5 weeks later was unsuccessful, as were seven sessions of plasma exchange undertaken over a 2-week period and the patient became tetraplegic. A 5-day course of alemtuzumab with pulsed IVMP was completed (week 9) but deterioration continued with decreased visual acuity (right eye: counting fingers, left eye: 6/36), vertigo and respiratory compromise requiring ventilatory support. MRI demonstrated new lesions (Fig. 1b). Repeat CSF revealed 10 lymphocytes and Aq4 was negative in serum and CSF. Alemtuzumab can take up to 3 months to take effect, however, in July 2011 (13 weeks after presentation) treatment was intensified due to continued decline and stem cells mobilised with CY 2 g/m plus G-CSF (10 lg/kg/day). Stem cell harvest was undertaken 2 weeks later. A second dose of CY (2 g/m) 4 weeks poststem cell harvest was followed by improvement—return of sensorimotor function to the left arm, cessation of vertigo and weaning from ventilatory support. Two months after first treatment with CY the patient underwent AHSCT using CY 200 mg/kg ? rabbit antithymocyte globulin (ATG, total dose 6 mg/kg). At this point she had an Expanded Disability Status Score (EDSS) of 8.5. Routine toxicity, including neutropenic sepsis, was managed and engraftment prompt. Four months from AHSCT, she could walk a few steps using parallel bars and had visual acuities of 6/24 (right) and 6/9 (left); EDSS 7.5. Repeat MRI demonstrated a stable lesion load (Fig. 1c). One year from the initiation of treatment with CY (8 months from AHSCT) she was able to walk 10 M with bilateral support, EDSS 6.5. Further imaging demonstrated no change. EBMT guidance [4] advises that patients with an EDSS score higher than 6.5 be excluded from AHSCT, except in instances of ‘malignant’ MS. Our patient had a rapid-onset demyelinating illness that we have termed malignant MS. We cannot exclude neuromyelitis optica (NMO), although Aq4 antibodies were consistently negative, including in CSF. In such cases, the distinction between MS, NMO and J. J. P. Alix (&) D. J. Blackburn B. Sharrack Sheffield Institute for Translational Neuroscience, University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK e-mail: j.alix@sheffield.ac.uk