INVESTIGATIONS

NeuroradiologyAmit A Roy

Katherine Miszkiel

AbstractNeuroradiology is the radiological subspeciality dealing with the diag-

nosis, characterization and, in some cases, treatment of disease entities

affecting the central or peripheral nervous system. It is a rapidly expand-

ing field and one in which technological advances have been pivotal in

driving further progression. The last few years have seen significant

improvements in access to high-quality imaging; modalities and tech-

niques that were once the remit of academic institutions with significant

research interests are now accessible to the majority with reduced cost,

improved availability and concomitant dissemination of expertise. The

trend towards subspecialization has continued in recent years, with

a specialist’s career choice no longer limited to the pursuit of either

a predominantly interventional or diagnostic role. The emergence of

those with dedicated expertise in head and neck imaging, paediatric

neuroradiology, neuro-ophthalmology, neuro-oncology and stroke is

a development that is likely to continue and parallels that which is occur-

ring in body imaging.

The objectives of this chapter are to introduce the principal neuroradio-

logical imaging modalities relevant to clinical practice, discuss what each

offers and convey their respective limitations. Scenarios in which a given

modality is particularly advantageous over others will be discussed as

well as the circumstances that preclude the use of certain techniques.

The list of modalities discussed is not intended to be exhaustive; the

emphasis will be on those that are currently routinely available but

novel developments and those currently limited to specialist centres func-

tioning mainly as research tools will also be mentioned briefly.

Keywords angiography; computerized tomography; Doppler ultrasound;

magnetic resonance imaging; myelography; perfusion imaging; positron

emission; radionuclide scanning

Introduction

Imagingmodalities fall into one of twomajor categories: those that

utilize ionizing radiation and those that rely instead upon some

other physical characteristic of the tissue being interrogated in

order to generate an image. The former group includes traditional

radiographic techniques, such as plain film radiography, angiog-

raphy and myelography, as well as the more recent developments

of radionuclide scanning and computed tomography (CT). The

Amit A Roy MBBS (Hons) BSc (Hons) MRCS DOHNS FRCR is a Neuroradiology

Fellow at the National Hospital for Neurology and Neurosurgery, Queen

Square, London, UK. Conflicts of interest: none declared.

Katherine Miszkiel BM (Hons) MRCP FRCR is a Consultant Neuroradiologist

at the National Hospital for Neurology and Neurosurgery, Queen

Square, London, UK. Conflicts of interest: none declared.

MEDICINE 40:8 440

latter subset includes magnetic resonance imaging (MRI) and

ultrasound.

MRI and CT are presently the modalities of choice in the

evaluation of CNS pathology, with radiography, myelography

and angiography generally regarded as second-line investiga-

tions, reserved for cases when the former are precluded or as

a prelude to therapeutic intervention. Despite being quick, rela-

tively inexpensive and portable, ultrasound presently has

a limited role in the evaluation of neurological disease on

account of the osseous skull vault, which is relatively impervious

to sound wave transmission. There are, however, a few defined

indications where ultrasound provides invaluable adjunctive

information.

In recent years, increasing scrutiny has been placed on the

judicious use of ionizing radiation in diagnostic studies. Well-

publicized incidents in which patients received radiation doses

from CT perfusion studies far in excess of those expected, with

consequent deleterious outcomes, have made this issue front-

page news in the medical press.1 Awareness and acknowledge-

ment of the ALARA principle, which dictates that diagnostic

studies utilize a radiation dose that is ‘as low as reasonably

achievable’ has always constituted a fundamental component of

radiology training. However, there has been progressive

dissemination of this message to the medical community as

a whole with the increasing expectation that tests be justified,

optimized and dose-limited. As such, there is now ever-greater

reliance on computerized post-processing techniques, which

ensure that image quality is maintained in the face of the need to

reduce radiation dose. The ‘image gently’ campaign,2 launched

in the USA in 2008 by The Alliance for Radiation Safety in

Paediatric Imaging, has sought to actively promote this message

specifically in relation to imaging the child and to date has

received over 12,000 pledges from medical practitioners.

Computed tomography

Since its inception in 1967 by the British engineer, Sir Godfrey

Hounsfield, interest in CT has exploded with progressive

refinements over the last four decades rendering the technique

invaluable in the diagnosis of neurological disease. Even today, it

remains the mainstay of imaging diagnosis in this field, not least

on account of its availability and speed; modern-day multislice

scanners, which can image multiple sites in the body simulta-

neously, are able to achieve exceptionally short scanning times,

facilitating the interrogation of ever smaller structures within

a practicable time period, and negating the effects of motion.

Indeed, the substantial evidence base that has recently been built

around the diagnosis and management of patients with stroke

owes a great deal to CT; its ready availability and rapid delivery

of high-quality diagnostic images has been fundamental to the

restructuring and centralization of stroke services, which has

recently revolutionized the management of this condition.

Technique

Conventional radiographic techniques involve the bombardment

of a subject with X-rays, produced by an X-ray tube. The image

generated is a representation of the extent towhich the component

tissues constituting the subject prevent the X-rays from passing

through, a property known as attenuation. The attenuation of

� 2012 Published by Elsevier Ltd.

INVESTIGATIONS

a material is inextricably linked to its density. In this way, a two-

dimensional (2D) representation of a 3D structure is obtained.

CT is a natural extension of this technique; the same under-

pinning physical principles are coupled with powerful computer-

processing power to culminate in a series of images, or slices,

depicting the subject concerned. Central to the understanding of

CT is the notion of ‘voxels’; these are volume elements analogous

to pixels in two dimensions. Each voxel depicts a small piece of

the patient being scanned and is assigned a unit of measurement,

called the Hounsfield unit, based on its attenuation. The

computer derives the average Hounsfield number of the voxel

under consideration via the fixed points of reference, namely the

values assigned for water (HU ¼ 0) and air (HU ¼ �1000).3 The

image begins taking shape as the numerical values for each pixel

are represented on a two-dimensional matrix by a shade of grey.

Tissues of high inherent density are depicted as white (such as

bone, calcification or intravenous contrast) whilst low-density

materials such as air and fat appear black. Soft tissue is of

intermediate density. It follows that this system allows for more

than 2000 shades of grey to be depicted. However, the human

eye is unable to differentiate between such subtle gradations

potentially rendering a large part of this dataset wasted. The

fundamental principle of ‘windowing’ circumvents this problem

and allows the user to tailor the image by focussing on a narrow

range of densities and disregarding all voxels with attenuation

values outside a pre-defined range. This principle is fundamen-

tally important in the interpretation of stroke imaging, as subtle

differences in the attenuation of ischaemic brain compared with

healthy tissue can be made conspicuous only through appro-

priate manipulation of windowing.

In recent years, the advent of multislice scanners has brought

huge advantages both in terms of improving image quality and

reducing scanning time. Present day scanners can assimilate up

to 256 sequential slices through a patient in a single rotation,

making imaging of the brain possible within a fraction of

a second. The attendant benefits in limiting artefact from motion

are huge. In addition, the speeds achievable are sufficient to

image during the first pass of a contrast bolus, obviating the need

for larger volumes that expose the patient to a potentially higher

risk of nephrotoxicity.

The ability to image faster and obtain thinner slices has also

made the notion of ‘isotropic’ voxels a reality. An isotropic voxel is

essentially a cube, dimensionally identical in all three planes. This

feature facilitates true 3D imaging through the generation of multi-

planar reformatted images that lose nothing in terms of resolution.

This is a major advance from the previous generations of CT

scanners, which could achieve this feat of high-resolution non-

axial imaging only by physically altering their gantry.

Contrast-enhanced CT (CECT)

CT of the brain is a rapid and powerful diagnostic tool with

proven benefit in both the acute and non-acute settings.

However, its efficacy can be improved in a number of scenarios

through the coupling of imaging with the administration of

intravenous contrast media. Contrast agents used in CT imaging

are water-soluble iodine macromolecules, either in ionic or non-

ionic forms. The latter represent a more recent development,

generally being the agents of choice today. Fewer associated

adverse effects are seen than when using ionic agents and this is

MEDICINE 40:8 441

thought to result from a reduced propensity to dissociate into

component molecules.

Although modern contrast agents are safe, adverse effects do

occur and include idiosyncratic reactions, anaphylaxis, drug

interactions and contrast-induced nephropathy. The rare but real

potential for anaphylactic reactions dictates that resuscitation

facilities are available wherever contrast-enhanced scanning is

being performed. Contrast-induced nephropathy is another

feared complication, accounting for 12% of cases of hospital-

acquired renal failure4; however, it is extremely unlikely in the

absence of recognized risk factors, such as pre-existing renal

impairment and severe diabetes.5 The choice of contrast agent in

the scenario of a patient deemed at high risk of nephropathy has

been the subject of much debate but current advice is that low-

osmolality, non-ionic media are safest.

The utility of contrast-enhanced imaging is in highlighting

areas where the bloodebrain barrier has lost its normal integrity,

as occurs in a number of infective, inflammatory and neoplastic

conditions. When an area of tissue takes up contrast, its density

(and thus the Hounsfield units ascribed to the voxels that depict

that area) also increases. As a consequence, the area of tissue

concerned appears brighter, a phenomenon termed enhance-

ment. The enhancement patterns of certain lesions are predict-

able and reproducible, thereby aiding differential diagnosis

(Figures 1e3).

As an adjunct to standard post-contrast imaging, a number of

other techniques utilizing intravascular contrast delivery have

evolved, simply by adjusting the timing of scanning relative to the

time of peripheral venous injection. CT angiography (CTA) and

venography (CTV) provide powerful non-invasive means by

which the vessels supplying and draining the central and periph-

eral nervous systems can be interrogated (Figures 4 and 5).

Indeed, CTA is often the primary investigation performed in

establishing the aetiology of subarachnoid haemorrhage, with

catheter angiography relegated to situations in which therapeutic

intervention is likely to ensue. The quality and speed with which

CTA can now be performed has also rendered it invaluable in the

assessment of stroke; it currently forms part of the initial imaging

protocol, such that patients can now undergo comprehensive

imaging of the brain and vasculature within minutes of arriving

through the emergency department’s door. This owes a great deal

to the advent of multislice scanners and powerful software

programs, which effortlessly reconstruct the datasets obtained

into formats that are most conducive to rapid diagnosis.

So-called ‘stealth’ or stereotactic CT scanning is another

relatively recent development. This permits pre-operative diag-

nostic imaging to be loaded into a system located in the operating

theatre, which translates the dataset into precise three-

dimensional images, thereby aiding surgical mapping and facil-

itating the safest and least invasive path to a lesion.

CT myelography combines the potential for high-quality

multi-planar reformatted imaging with the instillation of iodine-

based contrast media into the intrathecal space. The resulting

images enable excellent visualization of the terminal spinal cord

and caudal nerve roots. Conventional myelography, in which

plain radiography follows the instillation of contrast, is now

essentially defunct. CT cisternography employs a similar prin-

ciple and can be employed to visualize the CSF spaces around the

brainstem and thus the anatomy of the lower cranial nerves. MRI

� 2012 Published by Elsevier Ltd.

Figure 1 This 34-year-old woman had disseminated tuberculosis (TB) and multiple neurological signs and symptoms including headache, weakness and

lower cranial nerve palsies. (a and b) Coronal and axial post-contrast T1-weighted magnetic resonance (MR) images demonstrating obstructive hydro-

cephalus, multiple ring-enhancing tuberculomas (arrows) and prominent basal meningeal enhancement. (c) Sagittal post-contrast T1-weighted image of

the cervical spine demonstrates diffuse meningeal enhancement. Prominent enhancement involving the ventral surfaces of the pons and medulla

oblongata is particularly noteworthy (arrow). (d) Axial T2-weighted MR image through the thorax at the level of the upper mediastinum reveals multifocal

patchy pulmonary changes in keeping with active TB.

Figure 2 This 54-year-old woman presented with gradually progressive bony swelling involving the left side of her face. (a) Axial unenhanced CT on bony

windows demonstrates gross bony expansion, sclerosis and deformity involving the left fronto-temporal region. (b and c) Axial T2-weighted and stealth

protocol post-contrast T1-weighted magnetic resonance images show bony sclerosis and expansion, widening of the diploic space, subjacent dural

thickening and enhancement and normal intra-cranial appearances. The features are those of a predominantly intra-osseous meningioma.

INVESTIGATIONS

MEDICINE 40:8 442 � 2012 Published by Elsevier Ltd.

Figure 3 This 74-year-old man presented with rapidly progressive left sided weakness and clumsiness. (a and b) Axial T2-weighted magnetic resonance

images demonstrate thickening and signal abnormality in relation to the splenium of the corpus callosum (arrow) with further multifocal areas of

parenchymal hyperintensity involving the parieto-occipital regions bilaterally. (c and d) Multiple peripherally enhancing lesions on both sides of the

midline with involvement of the corpus callosum. The features are in keeping with multifocal high-grade glioma (glioblastoma multiforme).

INVESTIGATIONS

would now be more appropriate than either of these modalities in

the first instance, but they are invaluable adjuncts when MRI is

precluded.

CT perfusion is another relatively novel technique made

possible by the advent of faster scanning times. It is of particular

relevance in the field of stroke imaging as it permits the rate of

contrast uptake by defined areas of neuroparenchyma to be

quantified. The process culminates in graphical representations

of cerebral blood flow, blood volume and transit time from which

the distributions of infarcted tissue and potentially salvageable

ischaemic parenchyma can be derived.6 Although undoubtedly

efficacious, the technique remains principally a research tool,

limited to centres with experience and relevant expertise.

Magnetic resonance imaging

MRI is currently the modality of choice in the investigation of

neurological disease. It provides the greatest soft tissue

MEDICINE 40:8 443

resolution among the techniques presently available and does

not utilize ionizing radiation, rendering it safe in the vast

majority of scenarios. Since its inception in the 1970s, interest in

the technique has exploded, with progressive refinements and

the addition of novel sequences occurring in parallel with

concomitant advancements in CT. The two modalities are

frequently utilized in a complementary fashion, as there are

many circumstances in which the ready availability and scanning

speed of CT render it the more appropriate option.

Technique and principles7

Nuclear magnetic resonance (NMR), the fundamental principle

upon which MRI is based, was discovered as early as the 1930s.

However, it was not until Bloch and Purcell realized its signifi-

cance that NMR spectroscopy was born, their work culminating

in the award of the Nobel Prize for Physics in 1952. The exten-

sion of NMR to a medical imaging technique did not occur until

� 2012 Published by Elsevier Ltd.

INVESTIGATIONS

1973. Since this time, fervent research and development have

brought about huge advances and refinements to the technique,

elevating MRI to the status of current gold standard in imaging

technology.

NMR is based on the observation that isotopes with an odd

number of protons and neutrons demonstrate an intrinsic

magnetic moment and can thus be induced to resonate when

placed within a powerful magnetic field. The functional unit in

clinical MRI is the hydrogen nucleus, or proton, which is abun-

dant within organic tissue and behaves like a magnetic dipole

when placed within an electromagnetic field. During an MRI

scan, energy at a specific frequency is transmitted into the body

as radio waves, causing the abundant protons to resonate and

align against the magnetic field; when the radio wave then

ceases, the protons realign with the original magnetic field and

return energy in the form of further radio waves that constitute

the MR signal. This signal is progressively amplified and

undergoes numerous computer-processing steps to derive the MR

Figure 4 This 64-year-old woman presented with sudden onset of right-sided w

formed 24 hours later. (a) Axial unenhanced CT. No discernible hypodensity is s

ribbon appears intact. (b) Axial unenhanced CT. There is a short segment of hy

intraluminal thrombus (arrow). (c) Axial CT angiographic (CTA) image at the lev

internal carotid artery (ICA) just distal to the carotid bifurcation (arrow). (d) Axia

insular cortex (arrow). (e) Coronal fluid attenuated inversion recovery (FLAIR) MR

improved by nullifying the signal from adjacent CSF (arrow). (f) Diffusion-weighand white matter within the left MCA territory. (g) Corresponding apparent diff

temporal and parietal lobes is indicative of restricted diffusion and thus acute

thrombus within the left M2 segment corresponding to that seen on the admi

fat-suppressed imaging through the neck. (i) Maximum intensity projection (M

involving the left ICA just distal to the origin (black arrow). However, there is

arrow). A persistent trigeminal artery is an example of an arterial communicat

within the fetal circulation but normally involutes in adulthood. (j) Axial fat-suploss of the normal flow void on the left with signal hyperintensity in keeping wi

MEDICINE 40:8 444

image. Fundamental to the interpretation of MRI is the appreci-

ation that different body tissues comprise hydrogen atoms in

differing quantities and in varying molecular environments; the

nature of the resulting image thus reflects both the abundance of

hydrogen atoms and their chemical surroundings.

Basic sequences

The characteristics of the image obtained can be altered by

manipulating the magnitude and direction of the applied radio-

frequency pulses with pre-defined protocols termed sequences.

The so-called T1 and T2 relaxation times are the fundamental

parameters measured by all scanners, giving rise to T1- and T2-

weighted images respectively, the basic sequences central to

MRI.

T1-weighted images provide excellent anatomical resolution.

Free water molecules (such as those within circulating CSF)

appear of low signal (dark) whilst proteinaceous fluid and

melanin appear brighter than surrounding brain. Subacute

eakness. (aeh) Acute stroke protocol CT/CTA on admission and MRI per-

een in the left middle cerebral artery (MCA) territory and the cortical insular

perdensity within the Sylvian (M2) branch of the left MCA in keeping with

el of the pterygoid plates. There is no contrast opacification within the left

l T2-weighted MR image. Subtle signal hyperintensity is seen within the left

image. The conspicuity of parenchymal changes in the left insular region is

ted image (DWI): signal hyperintensity is demonstrated involving both grey

usion coefficient (ADC) image: signal hypointensity within the left insular,

infarction. (h) Axial gradient-echo T2* image demonstrates intraluminal

ssion unenhanced CT (arrow). (iek) MR angiography (MRA) and

IP) MRA images, antero-posterior (AP) projection. There is abrupt cut-off

reconstitution of the terminal ICA via a persistent trigeminal artery (white

ion between the carotid and vertebro-basilar systems, which are present

pressed T2-weighted image at the level of the proximal ICAs demonstrates

th intraluminal thrombus. (k) Right anterior-oblique (RAO) MIP MRA image.

� 2012 Published by Elsevier Ltd.

Figure 4 (continued)

INVESTIGATIONS

haemorrhage also appears bright due to the paramagnetic char-

acteristics of iron within methaemoglobin, giving rise to so-called

‘T1-shortening’. T1 images are also employed to demonstrate

contrast enhancement, which occurs with gadolinium-based

agents whose intrinsic ability to alter the magnetic properties

of blood is responsible for signal augmentation. The indications

for performing contrast-enhanced studies are analogous to those

in CT imaging.

T2-weighted images are superior in delineating abnormal

tissues such as those harbouring infection, inflammation and

neoplastic disease.

T2* images are optimized to assess the effects of molecules

with magnetic properties on surrounding tissues. The iron con-

tained within haemoglobin is the commonest example and

demonstrates paramagnetic effects following haemorrhage, which

alter the local magnetic field within its vicinity (Figures 4 and 6).

Scanning protocols

Typically, a routine brain scan comprises several sequences

including not only the above but also those tailored to the

specific indication. It is conventional to include all three

orthogonal planes (axial, coronal, sagittal), although any plane of

imaging is theoretically possible, unlike CT. Spinal scanning

typically includes sagittal imaging and selected axial slices

through any regions of interest.

There are a number of additional sequences that are particu-

larly advantageous in certain scenarios. For example, those that

suppress CSF-signal can be invaluable in visualizing the peri-

MEDICINE 40:8 445

ventricular lesions that characterize multiple sclerosis by

greatly improving their conspicuity. FLAIR (fluid-attenuated

inversion recovery) is such a sequence that has also proved to be

valuable in monitoring tumour follow-up.

Fat-suppressed sequences such as STIR (short-tau inverse

recovery) are images created with T2-weighting but with

suppression of signal generated by fat. This improves conspicuity

of entities such as oedema, where the high signal of fat may

obscure the boundaries of a pathological process. Fat-suppressed

axial imaging through the neck is frequently employed in

vascular dissection protocols, where the perceptibility of intra-

mural haematoma is improved. High spatial resolution tech-

niques such as CISS (constructive interference in steady state)

provide exquisitely detailed images of inner ear anatomy and the

lower cranial nerves, facilitating detection of even small

cerebello-pontine angle lesions, for example, without the use of

intravenous contrast. Establishing evidence of vascular contact

in suspected cases of trigeminal neuralgia or hemi-facial spasm

are further applications.

Diffusion-weighted imaging (DWI) utilizes the principle that

the signals generated by protons in water molecules differ

depending upon whether free diffusion is occurring; when

Brownian motion is not permitted due to pathological processes,

a differential MR signal is generated, which may be ‘mapped’.

In normal tissues or those in which vasogenic oedema occurs,

random Brownian motion of water molecules is not limited and

thus no diffusion restriction is seen. In tissues with a tight degree

of cellular packing or those in which cytotoxic oedema occurs,

� 2012 Published by Elsevier Ltd.

Figure 5 This 28-year-old woman presented with a history of headaches followed by progressive cerebral obtundation. There was a preceding history of

non-Hodgkin’s lymphoma. (a) Axial CT venogram (CTV) image at the vertex demonstrates irregular filling defects within the superior sagittal sinus

(arrows) with segments of non-opacification of the visualized cortical veins. The features are highly suggestive of sagittal sinus and cortical vein

thrombosis. (b) More inferiorly, a discrete filling defect is visible within the superior sagittal sinus e the ‘empty delta sign’ (black arrow). The superior

sagittal sinus is also expanded and hyperdense, suggestive of acute thrombosis. Scattered foci of para-sagittal parenchymal haemorrhage are also visible

(white arrows). (c) CTV midline sagittal maximum intensity projection image further demonstrates multiple filling defects within the superior sagittal sinus

(arrow). (d) Antero-posterior digital subtraction angiography (DSA) image depicting filling defects within the right transverse sinus and superior sagittal

sinus (arrows). A catheter has been placed within the right transverse sinus during attempted mechanical thrombectomy.

INVESTIGATIONS

restricted diffusion occurs and manifests as decreased signal on

apparent diffusion coefficient (ADC) mapping.

DWI has revolutionized the diagnosis of stroke, demon-

strating unequivocal changes within minutes of infarction, far

earlier than abnormalities are detectable on CT (Figure 4).

Changes classically persist for up to 3 weeks, which can be useful

in distinguishing acute from chronic phenomena. Restricted

diffusion is also a feature of cerebral abscesses, prion diseases

such as CJD8 and certain neoplastic lesions including lymphomas

and high-grade gliomas (Figure 7).

Magnetic resonance angiography (MRA) differs from the

equivalent CT technique in that it is possible non-invasively

to depict the vasculature without the need for contrast media.

This is based on the principle that protons within flowing

blood return signals distinct from those within static tissue.

Post-processing steps are able to extract these differences to

create so-called ‘time-of-flight’ angiographic images (Figure 4).

Selective depiction of the arterial or venous tree is possible.

MEDICINE 40:8 446

However, contrast-enhanced MRA (CEMRA) is increasingly

being performed for the diagnosis and follow-up of aneurysms

and other vascular malformations on account of its improved

resolution.

MR spectroscopy remains mostly the remit of research despite

early promise. Its basis lies in the ability of the MR signal to

provide quantitative information regarding chemical composi-

tion. Although the technique may be advantageous in certain

defined situations, such as the differentiation of recurrent

neoplasm from treatment-related change, and the assessment

and monitoring of the leukodystrophies,9 it has largely failed to

make a significant impact on routine clinical practice.

Novel developments and future directions

The intense research activity focused on MRI over the last four

decades shows no signs of diminishing with numerous advances

and technical refinements steadily adding to what is already

available in the world of clinical practice.

� 2012 Published by Elsevier Ltd.

Figure 6 This 66-year-old man had a history of previous head trauma and hypertension. (a) Axial unenhanced CT demonstrates a probable mature infarct

in the right occipital pole (white arrow) with likely gliotic change from trauma within the right inferior frontal lobe (black arrow). No obvious focus of

haemorrhage is seen. (bee) Phase, magnitude, maximum intensity projection and susceptibility-weighted imaging (SWI) images from the SWI protocol

demonstrate innumerable peripherally located microhaemorrhagic foci, lobar haemorrhage within the right frontal lobe and superficial haemosiderosis.

These features are seen typically in cerebral amyloid angiopathy. (f ) Gradient-echo T2* image fails to demonstrate a number of the microbleeds seen on

the SWI, highlighting the improved sensitivity of this novel technique.

INVESTIGATIONS

Presently, the majority of scanners in diagnostic use operate

at field strengths of 1.5 T (tesla). 3 T scanners are now relatively

commonplace but, despite definite advantages in terms of signal-

to-noise ratio, commensurate improvements in resolution are not

always apparent. In the research setting, higher field strength

magnets at up to 11 T are achievable, but legitimate safety

concerns and technical hurdles need addressing before such

equipment is used for clinical purposes.

Diffusion tensor imaging (DTI) is a novel development in

which both the magnitude and direction of diffusion within

cerebral white matter can be inferred and graphically repre-

sented, culminating in the generation of elegant tractographic

colour maps. Though principally a research tool confined to

centres with specific expertise, information such as this may be

fundamentally important to surgical planning in the future.10

Perfusion MRI, analogous in principle to the equivalent CT

method, entails scanning immediately and then sequentially after

injection of intravenous contrast. This technique has been coupled

with DWI in order to cross-reference areas of reduced perfusion

with corresponding restricted diffusion; in this manner, potentially

salvageable ischaemic parenchyma may be identified. Perfusion

MRI may also have a role in the discrimination of tumour recur-

rence from radiation necrosis and the predicting of malignant

transformation of low-grade gliomas through the detection of

MEDICINE 40:8 447

increases in cerebral blood volume over time. Other examples of

functional MRI include techniques in which dynamic scanning can

demonstrate areas of parenchyma intimately involved in speech,

through the depiction of increased activity. In the past, such tech-

niques have principally been research-oriented, but they are grad-

ually entering the realm of routine clinical practice as information

such as this may be invaluable to surgical planning.

Susceptibility-weighted imaging (SWI) is a novel MRI tech-

nique that is exquisitely sensitive to haemorrhage.11 Potential

clinical applications include the assessment of trauma, stroke,

malignancy and dementia (Figures 6 and 8).

‘Stealth’ and interventional MRI follow similar principles to

the analogous CT techniques; they not only facilitate surgical

mapping of lesions but also provide the means for real-time

imaging feedback intra-operatively.

Table 1 summarizes the advantages and disadvantages of CT

and MRI in neuroimaging. Box 1 lists some of the more common

contraindications and cautions associated with MRI.

Angiography and interventional neuroradiology

Intra-arterial cerebral angiography is usually achieved via selec-

tive catheterization of the carotid or vertebral arteries under

fluoroscopic guidance following percutaneous femoral or

� 2012 Published by Elsevier Ltd.

Figure 7 This 33-year-old man presented with rapidly progressive dementia. (a) Axial T2-weighted image at the level of the basal ganglia demonstrates

bilateral subtle signal hyperintensity involving the caudate and lentiform nuclei and thalami. (b) Axial fluid attenuated inversion recovery (FLAIR) image

demonstrates subtle cortically based signal hyperintensity involving the para-sagittal frontal lobes and peri-rolandic regions (arrows). (c and d) Axial

diffusion-weighted image (DWI) and apparent diffusion coefficient (ADC) map respectively: hyperintense change is seen within the basal ganglia and

thalami bilaterally with corresponding hypointensity on ADC; the appearances thus signify diffusion restriction. These are hallmark changes seen in

CreutzfeldteJakob disease (CJD).

INVESTIGATIONS

brachial artery puncture. Iodinated contrast medium is injected

rapidly through the catheter and sequential radiographic expo-

sures delineate the passage of the bolus through progressive

vascular phases. A digital subtraction technique removes bone

and other obscuring soft tissues, leading to a series of post-

injection images optimized to demonstrate the vascular

anatomy at multiple phases. Since the inception of this technique

some 80 years ago, numerous technological refinements

involving every step have occurred, including the engineering of

MEDICINE 40:8 448

the catheters, the safety of the contrast media and the sophisti-

cation of the fluoroscopic and image post-processing elements.

Powerful software applications are now able to transform the

dataset such that exquisite 3D representations of the most

complex vascular anatomy are possible, affording the operator

almost limitless potential to manipulate the images as desired.

Despite meticulous technique there remains the small but

significant risk of stroke through inadvertent arterial damage or

introduction of embolic foci. For this reason, catheter

� 2012 Published by Elsevier Ltd.

Figure 8 This 48-year-old woman presented with multiple transient ischaemic attacks (TIAs), dementia and progressive pseudobulbar palsy. (a) AxialT2-weighted magnetic resonance image depicts bilateral peri-ventricular and external capsular signal abnormality with a subcortical infarct in the left

parietal lobe (black arrow). (b) Coronal fluid attenuated inversion recovery (FLAIR) image demonstrating the same features. (c and d) Susceptibility-

weighted imaging (SWI) reveals multiple punctuate foci of signal hypointensity within the corpora striata, thalami and posterior fossa in keeping with

microhaemorrhages. This patient was suspected of suffering from CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and

leukoencephalopathy).

INVESTIGATIONS

angiography has largely been superseded by CTA or MRA, unless

the intention is to proceed with therapeutic intervention.

The burgeoning field of interventional neuroradiology has

arguably experienced the greatest advancement in recent times, and

owes a great deal to the huge technological stridesmadewithin both

the imaging and engineering sciences. Many conditions for which

surgery was the only feasible treatment 10e15 years ago can now

be treated successfully via a minimally invasive interventional

approach with significant improvements in morbidity and

MEDICINE 40:8 449

mortality. The range of therapeutic options is constantly evolving

and presently includes the exclusion of intra-cerebral aneurysms

through the delivery of endovascular platinum coils, the emboli-

zation of arteriovenous malformations and the treatment of cere-

bral vasospasm (Figures 5 and 9).

The advent of flow-diverting stents for aneurysms previously

deemed untreatable is another noteworthy advance. However,

advancements in the field of stroke treatment have been partic-

ularly exciting and so far-reaching as to prompt radical

� 2012 Published by Elsevier Ltd.

Advantages and disadvantages of CT and MRI in neuroimaging

Imaging modality Advantages Disadvantages

CT C Quicker scanning times

C Patient more accessible thus preferential

in critically ill or trauma patients

C Currently more sensitive in the assessment

of intra-cranial calcification, acute

haemorrhage and bony disease

C Improvements in 3D scanning with conse-

quent improvements in CT angiography

C Radiation dose, particularly important in

repeated scanning

C Inferior soft tissue contrast compared with

MRI

C Streak artefact from metallic implants

degrades image quality

MRI C No radiation burden

C Superior sensitivity in detecting CNS

pathology

C Ability to image in any plane without need

for reformatting

C Optimal soft tissue contrast

C Lengthy scanning time

C Requirements for general anaesthetic or

sedation in certain non-compliant groups

C Metallic foreign bodies contraindicated

(including medical devices such as cardiac

pacemakers and neurostimulators)

C First trimester of pregnancy is a relative

contraindication

Table 1

INVESTIGATIONS

restructuring of stroke service provision; the potential to deliver

thrombolytic agents directly to the site of blockage and deploy

mechanical thrombectomy devices directly to the site of occlu-

sion represents a huge change in the manner in which this

devastating condition is managed. Needless to say, rapid and

accurate diagnosis is a prerequisite; in this way, concomitant

advances in diagnostic CT and CTA have been equally

contributory.

Plain radiography

Plain radiographic techniques in neuroimaging have largely been

superseded by technically superior cross-sectional modalities.

Other than as part of a general skeletal survey, skull radiography

is now scarcely performed. Although spinal films are commonly

undertaken as part of follow-up after surgery, their role in initial

diagnosis is limited. Plain myelography is now largely defunct,

replaced by lumbo-sacral MRI as the modality of choice in the

Contraindications and cautions with MRI e metallicobjects or implants

C Pacemaker

C Implantable cardiac defibrillator (ICD)

C Aneurysm clips

C Coronary stents (some types)

C Metallic foreign bodies, particularly in or near the eye

C Metal implant, e.g. orthopaedic prosthesis

C Shrapnel or bullet wounds

C Neurostimulator

C Implanted drug infusion device

C Dentures/teeth with magnetic components

Box 1

MEDICINE 40:8 450

investigation of lower spinal pathology. In situations where MRI

is precluded, the myelographic technique is now combined with

CT to produce multi-planar images with superior diagnostic

potential.

Ultrasound

Although the osseous skull vault is relatively impervious to

sound wave transmission, a number of defined indications exist

in which ultrasound is particularly favourable, given the absence

of ionizing radiation and its portability, low cost and real-time

feedback potential.

Cervical Doppler (or duplex) has represented a key modality

in the evaluation of occlusive arterial disease within the neck

since the inception of ultrasound as a medical diagnostic tech-

nique. It represents a fast, portable, non-invasive and safe

alternative to intra-arterial angiography, which is now rarely

performed for this indication. The superimposition of Doppler

colour flow and velocity waveforms onto standard B-mode

sonographic imaging permits not only visualization of the

stenotic plaque and its anatomical composition but also quanti-

fication of velocity and pressure gradients.

Transcranial Doppler (TCD) is a more recent development. It

utilizes the principle that velocity measurements within the

major intra-cranial arteries are achievable via duplex ultrasound

performed through thinner bony landmarks such as the temporal

region or through the orbits. Recognized applications include the

assessment of intra-cranial stenosis, subarachnoid haemorrhage

(and potential associated vasospastic complications) and the

confirmation of brain death. Future developments may include

implantable devices linked to therapeutic drug delivery systems,

which may provide a means not only to detect stroke at the

earliest possible opportunity but also, potentially, to initiate

antithrombotic therapy.

Neonatal transcranial ultrasound is the most frequently per-

formed neuroimaging investigation in this age group, making use

� 2012 Published by Elsevier Ltd.

Figure 9 This 26-year-old woman presented with proptosis of the left globe and associated pulsatile swelling. (a and b) Axial T2-weighted magnetic

resonance imaging (MRI) scans depict gross proptosis of the left globe with a large curvilear flow void within the superior left orbit (arrow). (c) Lateral

digital subtraction angiography image following contrast injection via the left internal carotid artery (ICA) in the arterial phase. A prominent anteriorly

directed vessel (arrow) corresponding to that seen on the MRI opacifies via the cavernous carotid segment; the abnormal vessel is a distended left

superior ophthalmic vein and an underlying arteriovenous fistula is responsible. (d) Angiographic image following direct cannulation of the left superior

ophthalmic vein and instillation of embolic material at the origin of the fistula (arrow). Contrast injection via a catheter in the left ICA results in no

discernible flow through the previous fistulous communication.

INVESTIGATIONS

of the natural acoustic windows of the fontanelles. Its utility lies

principally in the bedside nature of the study, which makes its

deployment on the intensive care unit ideal. Modern-day scan-

ners may facilitate exquisitely detailed visualization of the

superficial neuroparenchyma. However, the technique is heavily

operator-dependent and its success relies wholly on the patency

and calibre of the fontanelles, which begin closing after 10

months or so. Limited visualization of the posterior fossa struc-

tures is a further limitation. Common indications include the

assessment of germinal matrix haemorrhage with its associated

deleterious sequelae.

Radionuclide imaging

In radionuclide imaging, a radiopharmaceutical (comprising

a tracer molecule coupled to a radioactive isotope) is adminis-

tered to the patient and imaging ensues following an appropriate

time interval, during which redistribution of tracer occurs. It is an

MEDICINE 40:8 451

example of functional imaging; biological processes such as

blood flow and metabolic activity can be inferred from the

distribution of tracer on the resulting image. Examples of

commonly used radionuclide techniques include FDG-PET

(fluoro-deoxyglucose positron emission tomography) and

HMPAO SPECT (hexamethypropyleneamine oxime single photon

emission computed tomography), the former enabling assess-

ment of cerebral metabolism and the latter depicting blood flow.

Common indications include the investigation of epilepsy and

dementia. In the former, areas of increased blood flow on the

ictal SPECT have been shown to correlate well with epileptogenic

foci. The evaluation of malignancy formerly constituted an

important indication for radionuclide scanning. The advent of

improved MRI and CT technology has all but obviated the need

to perform such tests in these cases, but FDG-PET may still play a

role in differentiating recurrent malignancy from post-treatment

change, a feat that has proved difficult with even the highest

quality anatomical imaging available.

� 2012 Published by Elsevier Ltd.

INVESTIGATIONS

Conclusion

Neuroradiology is a burgeoning field and one in which signifi-

cant recent technical advancements have occurred. It is rapidly

expanding in terms of manpower, expertise and resources such

that prompt access to the highest quality imaging is available to

all. Lengthy hospital admissions for diagnostic tests are no

longer a major factor and the emergence of interventional

neuroradiology is a development which has brought exciting

novel treatments to the fore and promises much for the near

future. A

REFERENCES

1 Safety Investigation of CT Brain Perfusion Scans: Initial Notification.

http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/

ucm185898.htm. Date Issued: October 8, 2009.

2 Goske MJ, Applegate KE, Bulas D, et al. Alliance for radiation safety

in pediatric imaging. Image gently: progress and challenges in

CT education and advocacy. Pediatr Radiol 2011; 41(suppl 2):

461e6.

MEDICINE 40:8 452

3 Dendy PP, Heaton B. Tomographic imaging. In: Dendy PP, Heaton B,

eds. Physics for diagnostic radiology. 2nd edn. London, UK: Taylor

and Francis Group, 1999; 249e276.

4 Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J

Kidney Dis 2002; 39: 930e6.

5 Pannu N, Wiebe N, Tonelli M. Prophylaxis strategies for contrast-

induced nephropathy. J Am Med Assoc 2006; 295: 2765e79.

6 Leiva-Salinas C, Provenzale JM, Wintermark M. Responses to the 10

most frequently asked questions about perfusion CT. AJR Am J

Roentgenol 2011; 196: 53e60.

7 Dendy PP, Heaton B. Magnetic resonance imaging. In: Dendy PP,

Heaton B, eds. Physics for diagnostic radiology. 2nd edn. London,

UK: Taylor and Francis Group, 1999; 378e406.

8 Vitali P, Maccagnano E, Caverzasi E, et al. Diffusion-weighted MRI

hyperintensity patterns differentiate CJD from other rapid dementias.

Neurol 2011; 76: 1711e9.

9 Saneto RP, Friedman SD, Shaw DW. Neuroimaging of mitochondrial

disease. Mitochondrion 2008; 8: 396e413.

10 O’Donnell LJ, Westin CF. An introduction to diffusion tensor image

analysis. Neurosurg Clin N Am 2011; 22: 185e96. viii.

11 Ong BC, Stuckey SL. Susceptibility weighted imaging: a pictorial

review. J Med Imaging Radiat Oncol 2010; 54: 435e49.

� 2012 Published by Elsevier Ltd.