ESTUDIO Y ANÁLISIS DE LOS VITRALES

FLAIR sequences were developed to improve lesion conspicuity. Lesions in the brain are

best seen on heavily T2 weighted CSE or FSE images, however the high signal from CSF

obtained with a heavily T2 weighted sequence creates partial volume effects and flow artefacts which can cause problems in lesion detection, particularly in the periventricular

and subcortical regions of the brain and in the spinal cord. The use of shorter echo times

reduces CSF signal but there is a loss of T2 weighting which is an important element of

the contrast between lesions and normal brain or cord. FLAIR sequences combine the suppression of CSF signal (due to a long inversion time) with heavy T2 weighting (long echo time).

Recent reports have suggested that the use of FLAIR sequences improves the detection

of MS lesions in the brain (De Coene 1992, Hajnal 1992), brainstem (De Coene 1993) and spinal cord (White 1992, Thomas 1993). The main problem of FLAIR is the long acquisition time, typically 12 minutes or more, hence fast FLAIR sequences have been developed. Preliminary studies of fast FLAIR (defined as inversion recovery prepared fast

spin echo) in MS have had conflicting results; some reporting a greater sensitivity to

brain lesions compared with FSE or CSE (Rydberg 1994, Hashemi 1995, Filippi 1996a) and others reporting no difference in sensitivity (Barratti 1995, Thorpe 1994). Experience with fast FLAIR in the spinal cord in MS has not been reported previously. The purpose

of the present study was to compare the sensitivity of fast FLAIR with FSE in both the brain and cord of patients with MS.

7.1.1 Study Design

The fast FLAIR technique used in this study is a development of that described by -122-

Rydberg which consisted of 5mm slices and a slice selective inversion pulse (Rydberg

1994). A standard inversion recovery sequence with interleaving of two sections

(sequential interleaving) and a 16 echo Rapid Acquisition with Relaxation Enhancement

(RARE) readout was utilised to decrease acquisition time. In order to reduce flow artefact caused by the pulsatile nature of non nulled CSF, a chopping phase encoding technique

was applied and the inversion pulse slice width was increased.

Ten patients with clinically definite MS (two RR, six SP and two PP; EDSS 2-8) and previously documented cord lesions were imaged with conventional T2 weighted FSE

in the axial plane resulting in 46 contiguous 3mm slices (TR= 2500ms, TEeff=48 and

96ms, echo spacing 12ms, in-plane resolution 0.9x1.25mm) in the brain and nine contiguous 3mm slices (TR=2500ms, TEeff=52 and 104ms, echo spacing 13ms, in-plane resolution 0.9x0.9mm) in the cervical cord. The fast FLAIR sequence acquired an

equivalent number of 3mm contiguous slices (TR=11,000ms, TI=2150ms, TEeff= 144ms, echo spacing 13ms, in-plane resolution 0.9x0.9mm), the acquisition time was 6 minutes 5 seconds in the brain and 7 minutes 44 seconds in the cervical cord.

Analysis. The FSE and fast FLAIR images were mixed and blinded for patient name.

Lesions were identified on the proton density images with cross reference to the T2

weighted images by two observers independently, who then reached a consensus on

number and site of lesions. Five sites were considered: spinal cord, posterior fossa, and in the cerebral hemisphere, discrete, periventricular and subcortical. Discrete lesions were

defined as those which were not contiguous with either the ventricles or cortex. The scans

were then compared for each patient and scored depending on whether lesions were seen on both sequences, FSE only, fast FLAIR only, FSE in retrospect or fast FLAIR in

retrospect for each of the four regions on every slice. Lesion identification was aided by

guidelines developed following examination of 40 fast FLAIR scans in normal controls

(Gawne-Cain 1997b). These primarily excluded symmetrical areas of increased signal in

the posterior internal capsule and periventricular areas, regions which are known to exhibit high signal on FLAIR.

Statistical analysis. Lesion detection rates in both sequences in different regions were

analysed using the non parametric Wilcoxon signed-ranks test.

7.1.2 Results

Analysis of the brain images showed additional cerebral hemisphere lesions in the

periventricular, discrete and subcortical areas in all patients with the fast FLAIR sequence compared with FSE (p< 0.03). On comparing the total number of lesions seen on each

sequence for each area (ie. FSE only + FSE in retrospect vs. fast FLAIR only + fast FLAIR in retrospect) fast FLAIR still demonstrated significantly more lesions in the periventricular and subcortical areas (p< 0.02). However in the posterior fossa more lesions were seen on the FSE images than on the fast FLAIR (p= 0.02, total including

lesions seen in retrospect p= 0.01) (see tables 7.1 and 7.2). Lesions in the cerebral hemispheres, which appeared discrete on the FSE images were often shown on the fast

FLAIR to be more extensive and confluent (see figure 7.1).

In the spinal cord, a total of 33 lesions were identified on the FSE images but only one

of these was seen on fast FLAIR alone and a further one on reviewing the FSE and fast

FLAIR images together (p< 0.001) (see table 7.2).

Table 7.1: Lesion detection in the brain and cord by FSE and fast FLAIR. FSE and fast FLAIR FSE only fast FLAIR only FSE in retrospect fast FLAIR in retrospect Total Discrete 266 (59.1%) 64 (14.2%) 120 (26.7%) 46 17 450 (100%) Peri­ ventricular 142 (56.8%) 18 (7.2%) 90 (36.0%) 14 8 250 (100%) Subcortical 62 (35.4%) 20 (11.4%) 93 (53.1%) 26 0 175 (100%) Posterior Fossa 4 (7.4%) 39 (72.2%) 11 (20.4%) 3 6 54 (100%) Spinal Cord 1 32 0 0 1 33

FSE only vs fast FLAIR only;

Discrete: p= 0.01, Periventricular: p< 0.001, Subcortical: p= 0.003, Posterior Fossa: p= 0.02, Spinal Cord: p< 0.001.

(FSE+FSE retro) vs (fast FLAIR+fast FLAIR retro);

Discrete: p= 0.1, Periventricular: p= 0.001, Subcortical: p= 0.01, Posterior Fossa: p=

0.01, Spinal Cord: p< 0.001.

Table 7.2: Lesion number by patient in the posterior fossa and spinal cord detected by

FSE and fast FLAIR.

Posterior Fossa Spinal Cord

Patient FSE and FSE fast FLAIR FSE and FSE fast FLAIR

fast FLAIR only only fast FLAIR only only

A 0 0 0 0 4 0 B 0 2 0 0 3 0 C 1 22(1) 1(2) 0 9 0 D 1 13 8(3) 0 6 0 E 0 1 0 0 1 0 F 0 0 0 0 2 0(1) G 0 1 0(1) 0 4 0 H 2 0(2) 2 0 2 0 I 0 0 0 0 1 0 J 0 0 0 1 0 0 Total 4 39 11 1 32 0

( ) refer to lesions seen in retrospect when the two sequences are compared directly.

m

4

Ki” iire 7.1: I'SH (left) and fast FLAIR (right) images oftiic cerebral hemispheres (top), posterior tbssa (middle) and spinal cord (bottom).

7.1.3 Discussion

By decreasing the signal from CSF, FLAIR sequences allow the use of longer TEs and hence more T2 weighting without compromising lesion visibility in the periventricular

or subcortical areas. Furthermore image degradation is decreased by reducing flow

artefacts. Using sequential interleaving and a 16 echo RARE readout the acquisition time

can be decreased to a suitable level whilst maintaining high resolution 3mm thick slices.

Optimisation of contrast is achieved by using longer TRs and TIs. The fast FLAIR sequences have been shown to be superior to standard FSE sequences in detecting lesions

in areas often difficult on FSE scans, particularly those at the grey/white matter interface

and around the ventricles where partial volume effects and higher CSF signal become significant. As in other studies of both FLAIR and fast FLAIR (Gawne-Cain 1997b), there was reduced grey/white matter contrast and diffuse high signal around the ventricles particularly the frontal and occipital horns, which did cause some difficulty with

identification of lesions within these areas, nevertheless CSF suppression was excellent and flow effects were minimal.

The aim of this study was to assess the relative efficacy of fast FLAIR imaging in the spinal cord and brain. Due to the problem of significant CSF flow artefacts, particularly in the cord, the sequence used by Reiderer was modified by increasing the inversion pulse

width to 2.2 times the slice thickness and changing the inversion time to 2150ms to allow

for the double inversion that then occurs. As in most previous studies fast FLAIR proved

to show significantly more lesions than FSE in the brain. However this study

demonstrates fast FLAIR to be inferior to standard FSE imaging in the detection of MS lesions in both the posterior fossa and spinal cord.

This finding is particularly relevant to the recent suggestion that fast FLAIR sequences

could supplant the conventional T2 weighted spin echo sequence as the basic screening

sequence for imaging of the brain and cord (De Coene 1993) and indicates that further

consideration is required before CSE is replaced.

Apart from poor lesion identification in the posterior fossa and spinal cord a further issue which may be relevant to the fast FLAIR sequence is that of measuring TLV, a key

component in many MS treatment trials. Quantitative lesion load measurement has not

been undertaken in this study but a potential difficulty with fast FLAIR could be the

diffuse high signal found around the frontal and occipital horns, which depending on lesion identification guidelines may either result in over-reporting of lesions or even under-reporting as small lesions may become lost amongst increased background signal.

Also as the RARE technique uses variable echo times, slight blurring of lesion edges in

the phase encoded direction of an image may occur which in theory means small lesions could be lost, although this may be balanced by increased intrinsic contrast of lesions in the heavily T2 weighted images (Constable and Gore 1992).

Although in terms of improving spinal cord imaging, this is a negative study, the result

is important in identifying the fact that lesions can not be presumed to be similar throughout the central nervous system. Consequently new MR sequences should not be

introduced into clinical practise until they have been validated throughout both the brain

and spinal cord. The fact that lesions are detected much less frequently in the posterior fossa and cord indicates that the lesions themselves are of different composition in

different sites. This observation is explored further in chapter eight, where T1 and T2

relaxation times are compared in controls and MS patients. By quantifying the actual characteristics of lesions through relaxation time measurements pathological specificity

will be improved enabling MRI sequences to be optimised for lesion detection.