Spinal Cord Lesions in Patients with Multiple Sclerosis: Comparisonof MR Pulse Sequences

Karl Hittmair, Reinhold Mallek, Daniela Prayer, Erwin G. Schindler, and Harald Kollegger

PURPOSE: To compare T2-weighted conventional spin-echo (CSE), fast spin-echo (FSE), short-tau inversion recovery (STIR) FSE, and fluid-attenuated inversion recovery (FLAIR) FSE se-quences in the assessment of cervical multiple sclerosis plaques.METHODS: Twenty patients withclinically confirmed multiple sclerosis and signs of cervical cord involvement were examined on a1.5-T MR system. Sagittal images of T2-weighted and proton density–weighted CSE sequences,T2-weighted FSE sequences with two different sets of sequence parameters, STIR-FSE sequences,and FLAIR-FSE sequences were compared by two independent observers. In addition, contrast-to-noise measurements were obtained. RESULTS: Spinal multiple sclerosis plaques were seen beston STIR-FSE images, which yielded the highest lesion contrast. Among the T2-weighted se-quences, the FSE technique provided better image quality than did the CSE technique, but lesionvisibility was improved only with a repetition time/echo time of 2500/90; parameters of 3000/150provided poor lesion contrast but the best myelographic effect and overall image quality. CSEimages were degraded by prominent image noise; FLAIR-FSE images showed poor lesion contrastand strong cerebrospinal fluid pulsation artifacts. CONCLUSIONS: The STIR-FSE sequence is thebest choice for assessment of spinal multiple sclerosis plaques. For T2-weighted FSE sequences,shorter echo times are advantageous for spinal cord imaging, long echo times are superior forextramedullary and extradural disease. FLAIR-FSE sequences do not contribute much to spinalimaging for multiple sclerosis detection.

Index terms: Sclerosis, multiple; Spinal cord, magnetic resonance; Magnetic resonance, compar-ative studies

AJNR Am J Neuroradiol 17:1555–1565, September 1996

5

Isolated spinal cord involvement occurs in15% to 20% of patients with multiple sclerosis(1). Magnetic resonance (MR) imaging hasproved to be the method of choice for depictingthese lesions (2–4). With standard T2-weightedconventional spin-echo (CSE) sequences, how-ever, intrinsic plaques can be detected in onlyabout 50% to 60% of multiple sclerosis patientswho have clinical findings that are highly sug-gestive of spinal cord lesions (2, 5). Recenthardware and software developments, such asmultiarray coils and fast spin-echo (FSE) se-quences, have improved the quality of spinal

Received January 2, 1995; accepted after revision March 12, 1996.From the Department of Neuroradiology (K.H., R.M., D.P., E.G.S.) and

the Clinic for Neurology (H.K.), University of Vienna (Austria).Address reprint requests to Dipl Ing Dr Karl Hittmair, Univ-Klinik f

Radiodiagnostik, AKH, Waehringer Guertel 18–20, A-1090 Vienna, Austria.

AJNR 17:1555–1565, Sep 1996 0195-6108/96/1708–1555

q American Society of Neuroradiology

15

MR images (6) and might also be advantageousfor depicting multiple sclerosis plaques. How-ever, the FSE technique offers a number of ad-ditional sequence parameters that influence im-age contrast, and the diagnostic efficacy of FSEsequences is therefore still subject to scientificinvestigation. Moreover, short-tau inversion re-covery (STIR) sequences and fluid-attenuatedinversion recovery (FLAIR) sequences havealso been introduced for MR imaging of the spi-nal cord (5, 7, 8) and have been reported toimprove the diagnostic efficacy of this tech-nique. FLAIR and STIR sequences can also ben-efit from the FSE technique (9, 10). Thus, anumber of imaging techniques are available forspinal cord imaging and for the assessment ofmultiple sclerosis plaques in particular. Thepurpose of this study was to compare the diag-nostic efficacy of T2-weighted FSE, STIR-FSE,and FLAIR-FSE sequences in the assessment ofcervical multiple sclerosis plaques and to com-5

pare these imaging techniques with a double-echo CSE sequence.

Subjects and MethodsTwenty patients (11 women and nine men; 22 to 55

years old; mean age, 33 years) with clinically confirmedmultiple sclerosis and signs of cervical cord involvementwere examined with MR imaging. Thirteen patients had arelapse-remission disease course, two patients had a pri-mary progressive disease course, and five patients had asecondary progressive course. The expanded disabilitystatus scale ranged from 1.5 to 7.5 (mean, 3.5).

MR examinations were performed on a 1.5-T supercon-ducting system using a multiarray spine coil. T2-weightedand proton density–weighted double-echo CSE se-quences, T2-weighted FSE sequences with two differentsets of sequence parameters, a STIR-FSE sequence, and aFLAIR-FSE sequence were obtained. The order of the se-quences was randomized for each patient. For sequencecomparison, only sagittal images with a field of view of 230mm and a matrix size of 256 3 204 were obtained. Be-cause a section thickness of 3 mm (which we use forroutine cervical FSE imaging) resulted in unacceptablyhigh levels of image noise on T2-weighted CSE images,4-mm-thick sections with a 10% intersection gap wereused for this study. This increases partial volume artifactsbut does not inhibit sequence comparison. The phase-encoding direction was anterior to posterior for the CSEsequence and feet to head for all FSE sequences. Presatu-ration pulses outside the field of view perpendicular to thephase-encoding direction and oversampling were used tominimize ghosting and fold-over artifacts. The anteropos-terior phase-encoding direction was chosen for CSE se-quences to curb fold-over artifacts that would have oc-curred with a single excitation and the feet-to-head phase-encoding direction. With a rectangular field of view, whichis suited for the anteroposterior phase-encoding directiononly, a second signal average was reasonable. For CSEsequences, a 60% rectangular field of view with a secondexcitation was used and provided a slightly higher signal-to-noise ratio than a quadratic field of view with only asingle excitation. For proton density–weighted and T2-weighted CSE sequences, the well-established parametersof 2500/15,90/1 (repetition time[TR]/echo time [TE]/excitations) were used.

Sequence parameters for all FSE sequences were op-timized in preliminary trials according to the results ofprevious publications and our own experience, as de-scribed below. The FSE technique offers a number ofadditional sequence parameters that influence image con-trast, as detailed for T2-weighted FSE sequences (11). Inour study, the initial T2-weighted FSE sequence was ob-tained with parameters that minimized contrast differencesrelative to the T2-weighted CSE sequence so that we couldevaluate the effects of the FSE technique only. Imageblurring has been observed for T2-weighted FSE se-quences with a long echo train length and short TEs (11)

1556 HITTMAIR

but this was not significant with echo trains shorter than 8.Thus, to resemble T2-weighted CSE contrast, an echotrain length of 8 was used and TR/effective TE was ad-justed to 2500/90. Conversely, longer TEs and longerecho trains have been advocated for FSE imaging of thecervical spine in a previous report (11). An optimization ofsequence parameters along the suggestions of this publi-cation led to a second T2-weighted FSE sequence with aTE of 150 and an echo train length of 24. This secondT2-weighted FSE sequence is routinely used in our insti-tution for evaluating degenerative disk disease. Corre-sponding to the TRs that were used, the first T2-weightedFSE sequence was termed FSE-2500 and the second FSE-3000.

The STIR-FSE sequence was altered for spinal cordimaging by slightly increasing the effective TE to 50 andreducing the inversion time to 110. The longer effective TEincreases T2 contrast relative to shorter TEs that are com-monly used for musculoskeletal STIR imaging. The shorterinversion time reduces scan time because of a shorterdead time during the inversion time interval. A shorterinversion time also reduces fat suppression, but this isundesirable for cord imaging. The synergistic effects oflong T1 and T2 relaxation that yield a high lesion contraston STIR images are preserved with short inversion times(12). An asymmetric incomplete k-space sampling (oneecho collected before the effective TE and six echoescollected thereafter), an echo train length of 8, and sixsignal averages were found to provide good overall imagequality for STIR-FSE images in preliminary trials.

We did not find many reports in the literature aboutsequence parameter optimization of FLAIR-FSE se-quences (10). The sequence parameters for the FLAIR-FSE sequence used for this study were determined asfollows: For the suppression of the cerebrospinal fluid sig-nal, an inversion time of 2000 yielded the best results. Thelong dead time during the inversion time interval increasesscan time and must be compensated by a long echo trainthat can be used only with a long effective TE. Conversely,in our experience with FLAIR-FSE imaging of the brain,very long values for effective TE (of 150 or more) mightreduce the contrast of some type of lesions. In preliminarytrials, the best results in terms of overall image quality,lesion detectability, and scan time were provided by aneffective TE of 120, which enabled an echo train as long as18 and thus three excitations within a reasonable scantime. This set of sequence parameters for FLAIR-FSE isused for routine spinal imaging in our institution and wasalso used for this study. The individual sequence param-eters and the scan times of all sequences used are listed inTable 1.

Technicians were advised to use a window setting thatprovided optimal visibility of the spinal cord lesion and toadjust the contrast of the individual sequences as much aspossible. The individual sets of images were then assessedside by side independently by two experienced neuroradi-ologists. Since contrast differences were obvious, the in-terpreters could not be completely blinded to the type ofsequence. In two patients, a previous MR examination

AJNR: 17, September 1996

TABLE 1: MR sequence parameters compared

Proton Density–Weighted CSE

T2-WeightedCSE

T2-WeightedFSE-2500

T2-WeightedFSE-3000

STIR-FSE FLAIR-FSE

TR 2500 2500 2500 3000 2165 6000TE (effective) 15 90 90 150 50 120Inversion time . . . . . . . . . . . . 110 2000Echo train length . . . . . . 8 24 8 18Excitations 2 2 6 6 6 3Scan time 10 min, 44s 10 min, 44 s 6 min, 25 s 5 min, 12 s 6 min, 34s 7 min

Note.—CSE indicates conventional spin-echo; FSE, fast spin-echo; STIR, short-tau inversion recovery; and FLAIR, fluid-attenuated inversionrecovery.

AJNR: 17, September 1996 MULTIPLE SCLEROSIS 1557

obtained during an acute phase of the disease was avail-able and was compared with the recent MR examination.Image assessment criteria were lesion detectability (num-ber and contrast of lesions, with number of lesions consid-ered more important); lesion extension; lesion delimita-tion; myelographic effects (cerebrospinal fluid/cordcontrast and homogeneity of cerebrospinal fluid, evalu-ated for “bright cerebrospinal fluid” sequences only); andoverall image quality (image noise, visibility of small an-atomic details, image degradation by artifacts). For everypatient, a ranking of sequences was established indepen-dently with regard to the individual image assessmentcriteria (ranked 1 for the best sequence). Sequences werethen compared for both readers independently by usingthe nonparametric version of the Student-Newman-Keulstest (13). In addition, ghost artifacts from patient motion(swallowing, cardiac pulsation, respiration, blood flow),from cerebrospinal fluid flow, and from truncation-typeartifacts were classified as absent or not disturbing (0) oras definitely reducing the diagnostic efficacy (1).

For objective image assessment, contrast-to-noise ra-tios between normal cord andmultiple sclerosis plaques aswell as between cerebrospinal fluid and normal cord weredetermined: the signal intensity of the different anatomicstructures was assessed by using region-of-interest mea-surements, with the regions of interest placed identicallyon the different sequences. Differences between signal ofnormal cord (Scord), signal of multiple sclerosis lesions(Slesion), and signal of cerebrospinal fluid (SCSF) were thenrelated to the standard deviation (SD) of background airmeasured at areas free of ghost artifacts (SDair)

SCNRlesion(CSF) 5Slesion (CSF) 2 Scord

SDairD

(14). Contrast-to-noise ratios (CNRs) of the individual se-quences were then compared with one another by meansof paired one-tailed t tests (P , .05). Since scan timeswere similar, contrast-to-noise ratios were not related toscan time. Scan time for the FSE sequences were between5 minutes 12 seconds and 7 minutes, the CSE took abouttwice as long (11 minutes 44 seconds) but also providedtwo types of images (proton density–weighted and T2-weighted) simultaneously.

Results

Signal abnormalities within the cervical orupper thoracic cord were found in 17 (85%) of20 patients. In all three patients without spinalcord signal abnormalities, MR images of thebrain showed demyelinating lesions, whichcould explain the clinical findings that were at-tributed primarily to suspected spinal cord le-sions. The expanded disability status scale ofthese three patients was low (1.5, 2.5, and 3.0,respectively), all three patients had a relapsing-remission disease course, and the duration ofthe disease from the time of its onset was short(1 month, 5 months, and 4 years, respectively).Different types of lesions were observed, fromsmall circumscribed foci with markedly in-creased signal on all types of sequences to largeand poorly marginated areas with only subtlesignal abnormalities.

Spinal Cord Lesion Assessment

Intrinsic spinal cord lesions were seen best onSTIR-FSE images (Figs 1–3), which were par-ticularly superior in cases of large, poorly mar-ginated plaques with only subtle signal abnor-malities (Figs 3 and 4); these types of lesionswere hardly visible on any other type of images.Lesions showed the highest contrast, appearedlarger, and were better delimited on STIR-FSEimages. In six patients, additional plaques weredepicted on STIR-FSE images that would havebeen missed on the other types of images.In two patients for whom a previous MR ex-

amination obtained during an acute phase ofthe disease was available and showed acutehigh-intensity multiple sclerosis plaques on T2-weighted images, those multiple sclerosisplaques showed a markedly lower contrast onthe T2-weighted images of the follow-up exam-ination. Clinically, the decrease of T2 contrast

Fig 1. Thirty-one-year-old man with multiple sclerosis.STIR-FSE image (A) shows high-intensity plaque within the cervical cord at the C1–2 level and a second less bright lesion at C-3.

Both multiple sclerosis plaques show a lower contrast on the T2-weighted FSE-2500 image (B). Detectability of the C1–2 lesion is furtherreduced on the T2-weighted FSE-3000 image (C), on which the C-3 lesion is hardly visible, despite the best overall quality of all images.The T2-weighted CSE image (D) is degraded by prominent image noise, which greatly complicates the detection of the lesion at C-3,whereas the C1–2 lesion can be delineated. The T2-weighted FSE-3000 image (D) shows the best myelographic effect, with the brightestand most homogeneous cerebrospinal fluid, which is advantageous for the assessment of the disk protrusion at C5–6. Cerebrospinal fluidappears dark on proton density–weighted CSE (E) and FLAIR-FSE (F) images. Lesion contrast is poor on both of these dark-cerebrospinal-fluid sequences, but is slightly better on the proton density–weighted CSE image.

1558 HITTMAIR AJNR: 17, September 1996

Fig 2. Twenty-year-old woman with multiple sclerosis.STIR-FSE image (A) shows a poorly marginated area of increased signal at C2–3. This plaque is less well seen on T2-weighted

FSE-2500 (B) and proton density–weighted CSE (C) images, poorly seen on the T2-weighted CSE image (D), and not seen reliably onT2-weighted FSE-3000 (E) and FLAIR-FSE (F) images. The cerebrospinal fluid signal is brightest and most homogeneous on theT2-weighted FSE-3000 (E) image; the FLAIR-FSE (F) image is degraded by extensive cerebrospinal fluid pulsation artifacts, whichcause a high cerebrospinal fluid signal within large areas of the cervical subarachnoid space.

AJNR: 17, September 1996 MULTIPLE SCLEROSIS 1559

Fig 3. Twenty-eight-year-old woman with multiple sclerosis.STIR-FSE image (A) shows diffuse multiple sclerosis involvement, whereas a good-

quality T2-weighted FSE-3000 image (B) shows no definite signal abnormality within thecervical cord.

Fig 4. STIR-FSE image in a 29-year-oldman with multiple sclerosis but without def-inite signal abnormalities within the cervicalcord on any sequence. In contrast to thewidespread areas of increased signal withinthe cervical cord seen in Fig 3A, this “nor-mal” STIR-FSE image shows a homoge-neous low-signal-intensity cervical cord.

1560 HITTMAIR AJNR: 17, September 1996

was paralleled by a significant improvement insymptoms. At the follow-up examination, thelesions were barely visible on the FLAIR-FSEand CSE images but still excellently depicted onthe STIR-FSE images.The mean contrast-to-noise ratio between

multiple sclerosis plaques and normal cord wasabout twice as high on STIR-FSE images as onany other sequence (highly significant t tests)(Table 2). The differences between the meancontrast-to-noise ratio of the remaining se-quences were much lower. Intermediate con-trast-to-noise ratios were found for T2-weightedFSE-2500 and T2-weighted CSE images, whilethe lowest contrast-to-noise ratios were foundfor T2-weighted FSE-3000, proton density–weighted CSE, and FLAIR-FSE images. TheCNR values of the individual sequences and thestatistically significant differences between theindividual sequences (as tested with paired one-tailed t tests, P , .05) are listed in Table 2. Theanalysis of the subjective image assessment cri-teria provided very similar results for both read-ers (without significant interobserver variability)and paralleled the results of CNR measure-ments. The rank sums of lesion detectability,lesion extension, and lesion delimitation wereranked in the same order and were significantly

higher for STIR-FSE images than for any othersequence (Student-Newman-Keuls test, P ,.05). The T2-weighted FSE-2500 sequence wassecond, followed by the T2-weighted CSE andthe proton density–weighted CSE; reader 1 feltslightly more comfortable with T2-weightedCSE sequences, whereas reader 2 slightly pre-ferred proton density–weighted CSE sequences.Regarding lesion characterization, the T2-weighted FSE-3000 sequence was rated inferiorto even the CSE sequences by both readers, theFLAIR-FSE sequences were least desirable.

Overall Image Quality, Artifacts, andMyelographic Effect

Both readers rated the overall image qualityof the T2-weighted FSE-3000 sequence as best(significant Student-Newman-Keuls test, P ,.05), because this type of image was almostfree of distortion artifacts and showed the leastimage noise, the best myelographic effect, andgood visibility of small anatomic detail withno noticeable image blurring. The overallimage quality of STIR-FSE and T2-weightedFSE-2500 sequences was rated as significantlyinferior (Student-Newman-Keuls test, P ,0.05)to the T2-weighted FSE-3000 sequence by both

readers but still as very good. The STIR-FSEimages showed some image blurring which,however, did not compromise the diagnosticefficacy even for the smallest multiple sclerosisplaques. The T2-weighted FSE-2500 imageshad a slightly increased image noise as com-pared with the T2-weighted FSE-3000 images,and the cerebrospinal fluid was less bright andless homogeneous on this type of image. Amarkedly and significantly lower overall imagequality was found for the FLAIR-FSE and protondensity–weighted CSE sequences but withoutsignificant differences between these two se-quences (Student-Newman-Keuls test, P ,.05). Overall image quality of the T2-weightedCSE sequence was rated lowest by both readers(significant Student-Newman-Keuls test, P ,.05). FLAIR-FSE images were degraded by dis-turbing artifacts from cerebrospinal fluid pulsa-tions and by image noise. On FLAIR-FSE im-ages, cerebrospinal fluid signal was nothomogeneously suppressed but showed a highsignal in some areas, particularly in compart-ments of the subarachnoid space with a prom-inent flow void on bright-cerebrospinal-fluid im-ages. This complicated image analysis and wasthought to have reduced diagnostic efficacy in13 cases. The flow voids on bright-cerebrospi-nal-fluid images were considered to have defi-nitely reduced the diagnostic efficacy only onthe STIR-FSE images of one patient but in noneof the other images. Overall image quality ofCSE images was affected by pronounced imagenoise, while the proton density–weighted CSEimages were less severely degraded than theT2-weighted CSE images. Ghost artifacts defi-nitely reduced the diagnostic efficacy of CSEimages in four patients (T2-weighted CSE im-ages in four patients and proton density–weighted CSE images in three patients). Trun-cation-type artifacts were noticeable on CSEand FSE images, but were not thought to havedefinitely reduced the diagnostic efficacy of anyimage.The myelographic effect was assessed for the

bright-cerebrospinal-fluid sequences only. Thecerebrospinal fluid appeared brightest and mosthomogeneous on T2-weighted FSE-3000 im-ages, which was reflected by the best subjectiveranking by both readers (significant Student-Newman-Keuls test, P , .05) and by the highestcontrast-to-noise ratio between cerebrospinalfluid and normal spinal cord (significant pairedone-tailed t test, P , .05) (Table 3). The supe-

TABLE

2:Contrast-to-noise

ratios

ofMSplaques

STIR-FSE

T2-WeightedFSE-2500

T2-WeightedCSE

T2-Weighted

FSE-3000

FLA

IR-FSE

Proton

Density–W

eightedCSE

Meancontrast-to-noise

ratio

(lesion/norm

alcord)

13.87

7.43

6.46

5.64

4.69

3.97

Statisticallylower

than:*

...

STIR-FSE

STIR-FSE

STIR-FSE,T2-

weightedFSE-

2500

STIR-FSE,T2-weighted

FSE-2500,

T2-

weighted-CSE

STIR-FSE,T2-

weightedFSE-2500,

T2-weightedCSE

Statisticallyequalto:*

...

T2-weightedCSE

T2-weightedFSE-

2500,T2-weighted

FSE-3000

T2-weighted,

FLA

IR-

FSE,proton

density–w

eighted

CSE

T2-weightedFSE-3000,

proton

density–w

eightedCSE

T2-weightedFSE-

3000,FLA

IR-FSE

Statisticallyhigher

than:*

T2-weightedFSE-2500,

T2-weightedCSE,T2-

weightedFSE-3000,

FLA

IR-FSE,proton

density–w

eightedFSE

T2-weightedFSE-3000,

FLA

IR-FSE,proton

density–weightedCSE

FLA

IR-FSE,

proton

density–

weighted

...

...

...

Note.—STIR

indicatesshort-tauinversionrecovery;FSE,fastspin-echo;

CSE,conventionalspin-echo;andFLA

IR,fluid-attenuatedinversionrecovery.

*Differencesof

contrast-to-noiseratioswereanalyzed

byusingpaired

one-tailedttests(P

,.05).

AJNR: 17, September 1996 MULTIPLE SCLEROSIS 1561

TABLE 3: Myelographic effect

T2-Weighted FSE-3000T2-WeightedFSE-2500

STIR-FSE T2-Weighted CSE

Mean contrast-to-noise ratio 41.22 20.90 18.01 14.05Statistically lower than:* . . . T2-weighted

FSE-3000T2-weighted FSE-3000 T2-weighted FSE-3000,

T2-weighted FSE-2500, STIR-FSE

Statistically equal to:* . . . STIR-FSE T2-weighted FSE-2500 . . .Statistically higher than:* T2-weighted FSE-2500,

STIR-FSE, T2-weighted CSE

T2-weighted CSE T2-weighted CSE . . .

Note.—FSE indicates fast spin-echo; STIR, short-tau inversion recovery; and CSE, conventional spin-echo.* Differences of CNRs were analyzed by using paired one-tailed t tests (P , .05).

1562 HITTMAIR AJNR: 17, September 1996

rior myelographic effect allowed an excellentassessment of degenerative disk disease, whichwas found in six patients (Fig 1). Contrast-to-noise ratio measurements and subjective imageassessment revealed that the myelographic ef-fect of T2-weighted FSE-2500 and STIR-FSEsequences was significantly inferior to the T2-weighted FSE-3000 sequence but not signifi-cantly different from each other; T2-weightedCSE was significantly inferior to all other se-quences (Student-Newman-Keuls and pairedone-tailed t tests at P , .05, respectively).Despite the statistically significant differences,the myelographic effects on T2-weighted FSE-2500 and STIR-FSE images were still goodenough to facilitate an exact evaluation of de-generative disk disease. T2-weighted CSE im-ages were markedly inferior in this regard be-cause of the pronounced image noise. Theevaluation of disk protrusions was most difficulton dark-cerebrospinal-fluid images, such as onproton density–weighted CSE and FLAIR-FSEimages, because the degree of narrowing of thespinal canal and the cerebrospinal fluid spacecould not be assessed reliably.

Discussion

Although MR imaging is the only imagingmethod suitable for the assessment of spinalcord multiple sclerosis plaques, its diagnosticsensitivity is still not sufficient when a conven-tional imaging technique is used, as only a lim-ited percentage of these lesions can be seen (2,5). This is a major diagnostic drawback, be-cause 15% to 20% of spinal multiple sclerosislesions occur without MR signal abnormality inthe brain (1) and in these cases, a radiologicdiagnosis cannot be established on the basis ofbrain MR findings. Although it is commonly ac-

cepted that the FSE technique improves theappearance of MR images, experience with FSEin imaging of the spinal cord is limited, whereasthere is long-term, extensive experience withCSE sequences. With the CSE technique, com-monly the anteroposterior phase-encoding di-rection is used, while with the FSE technique,multiple excitations and the feet-to-head phase-encoding direction are reasonable. Our resultsfavor the feet-to-head phase-encoding directionused for FSE sequences, because it avoided theghost artifacts seen on the CSE images. Other-wise, differences between the CSE and FSE se-quences and differences between the individualFSE sequences can be attributed to the differentsequence techniques and to different sequenceparameters. Established sequence parametersfor T2-weighted CSE and proton density–weighted CSE sequences are 2500/15,90; se-quence parameters for FSE sequences are lesswell established. To facilitate a fair comparisonof optimized sequences, parameters for all FSEsequences had been optimized in preliminarytrials along the suggestions of previous publica-tions. A significant reduction of image noise andscan time were the greatest merits of the FSEtechnique. However, it could be shown that thereduced image noise does not necessarily im-prove diagnostic efficacy, as discussed below.With regard to lesion detection and charac-

terization, the results of the contrast-to-noiseratio measurements and the subjective imageassessment provided concordant results. TheSTIR-FSE sequence was considered the best inthis regard, which is particularly important be-cause STIR-FSE images showed multiple scle-rosis plaques that would have been missed onthe other types of images. In three patients,even STIR-FSE images revealed no definite sig-nal abnormality. These cases, however, need

AJNR: 17, September 1996 MULTIPLE SCLEROSIS 1563

not necessarily represent false-negative MR re-sults, because the clinical symptoms that hadfirst fostered suspicion of spinal cord involve-ment could also be attributed to demyelinatinglesions of the brain seen on cranial MR images.Thus, the STIR-FSE sequence, together withrecent hardware developments used for thisstudy, provides a high sensitivity for cervicalmultiple sclerosis plaques that significantly ex-ceeds previously published data (2, 5). Thehigh lesion contrast on STIR-FSE images canbe attributed to the synergistic effect of pro-longed T1 and T2 relaxation times (12), whichcharacterize not only spinal cord plaques butalso most other types of pathologic tissue (15).With all other types of sequences used for thisstudy, prolonged T1 and T2 relaxation timesproduce antagonistic effects, and this reduceslesion contrast. The synergistic effect of long T1and T2 are particularly advantageous in lesionswith only slightly prolonged T2 relaxation times,which might be characteristic of inactive multi-ple sclerosis plaques. In two of our patients, afollow-up examination of active multiple sclero-sis plaques revealed a marked signal decreaseon T2-weighted images, which was paralleledby a significant clinical improvement. The inac-tive plaques, with only low T2-contrast, bene-fited particularly from the synergistic T2- andT1-contrast on the STIR-FSE images. Com-pared with conventional STIR sequences, themerits of the STIR-FSE sequence are an im-proved overall image quality and reduced scantimes without relevant changes of the uniqueSTIR contrast (9). The slight blurring that wasobserved on the STIR-FSE images in this studycan be attributed to a significant T2 decay dur-ing k-space sampling (11). This might havebeen reduced with longer TEs, but longer TEsmight have also reduced the conspicuity ofsome multiple sclerosis plaques. Results of thetwo T2-weighted FSE sequences indicate thatlong TEs are inadequate for seeing multiplesclerosis plaques, which we discuss in a moredetailed way below. The slight blurring seen onthe STIR-FSE images was a negligible problemas compared with the high lesion contrast, abil-ity to detect small lesions, and excellent delim-itation of lesions it afforded.The two T2-weighted FSE sequences pro-

vided good image quality; the T2-weightedFSE-2500 sequence was equal to the STIR-FSEsequence, and the T2-weighted FSE-3000 wassuperior to the STIR-FSE sequence in this re-

gard. However, lesion conspicuity on T2-weighted FSE sequences was markedly lowerthan that on STIR-FSE images. This is impor-tant, because readers might feel comfortablewith a false-negative diagnosis derived fromgood-quality images. There was also a signifi-cant difference in lesion conspicuity betweenthe two sets of T2-weighted FSE sequences.The T2-weighted FSE-3000 sequence showedthe best overall image quality but was signifi-cantly inferior to the T2-weighted FSE-2500 se-quence with regard to lesion characterizationbecause of lower lesion contrast, smaller lesionextension, and inferior lesion delimitation. OnT2-weighted FSE-3000 images, spinal multiplesclerosis plaques were masked despite the ex-cellent overall image quality, and intrinsic cordplaques were even less visible than they were onCSE images, with greatly inferior overall imagequality. Image blurring has been discussed asan explanation for the reduced contrast, partic-ularly in regard to small lesions on FSE se-quences (16). Some findings, however, suggestthat the differences between the two T2-weighted FSE sequences of this study might bedue to a different T2-weighting (caused by adifferent effective TE) rather than to image blur-ring. First, no image blurring was noticeable onT2-weighted FSE-3000 images. Second, therewas no difference between small and large le-sions. Third, a poorer delimitation on T2-weighted FSE-3000 images was always paral-leled by lower lesion contrast. The maximalsignal difference between two types of tissuewith different T2 relaxation times is observed atan optimal TE that depends on the actual dif-ference of T2 (10). With only slightly prolongedT2 relaxation times that might be characteristicof inactive multiple sclerosis plaques, the signalof normal cord and pathologic lesions will havealready decreased at a long TE. In these cases,shorter TEs can produce a higher contrast be-tween normal cord and pathologic lesions, be-cause lesion signal is still preserved. The valueof shorter TEs for seeing multiple sclerosisplaques has already been observed by otherinvestigators (5, 7). Conversely, it is known thatlong TEs with long echo trains provide a supe-rior myelographic effect and a better overallimage quality. This has been advantageous forthe assessment of degenerative disk disease(11) and was also confirmed by the results ofour T2-weighted FSE-3000 sequence (11).FLAIR-FSE sequences were of minor diag-

nostic value for imaging cervical multiple scle-rosis plaques. Considering both the results ofcontrast-to-noise ratio measurements and sub-jective image assessment, the FLAIR-FSE se-quence was worst or among the worst in thisregard. FLAIR images not only were degradedby an incomplete cerebrospinal fluid signal sup-pression but also resulted in insufficient lesioncontrast. CSF flow artifacts have already beenobserved on multisection FLAIR-FSE se-quences that commonly use section-selectiveinversion pulses (10). Since cerebrospinal fluidpulsations are present in the cervical subarach-noid space, spins that do not “see” the inversionpulse enter the section during the inversion timeinterval and produce a high cerebrospinal fluidsignal with the heavily T2-weighted FSE se-quence that follows the inversion time interval.CSF pulsation artifacts were not observed onthe conventional FLAIR sequence reported byThomas et al (5) because a non–section-selec-tive inversion pulse was used in that investiga-tion. With a non–section-selective inversionpulse, however, each section “sees” a differentinversion time interval. For sagittal cord imag-ing, in which the entire cord is covered with afew sections, this seems to be only a minorlimitation (8), and a non–section-selective in-version pulse might be useful to reduce cere-brospinal fluid pulsation artifacts in multisectionFLAIR-FSE imaging. Cardiac synchronization isan alternative approach to this problem and hasbeen shown to be effective in reducing cerebro-spinal fluid pulsation artifacts with T2-weightedCSE sequences (17). In addition to the cerebro-spinal fluid pulsation artifacts, poor lesion con-trast is another drawback of the FLAIR-FSE se-quence with regard to assessment of multiplesclerosis plaques. Since the FLAIR-FSE se-quence consists of an inversion pulse followedby a heavily T2-weighted FSE sequence, theexplanation for the poor plaque contrast onFLAIR-FSE images seems to be the long effec-tive TE and echo train length, analogous to theT2-weighted FSE-3000 sequence. This appearsto be a major limitation of FLAIR-FSE se-quences in general, because the long dead timeduring the inversion time interval (about 2000milliseconds needed for cerebrospinal fluid sup-pression) necessitates a fast data acquisition bythe FSE sequence, and a fast data acquisitionrequires long echo trains and a long effectiveTE. In addition, the inversion pulse of FLAIRsequences introduces a considerable T1

1564 HITTMAIR

weighting, which acts antagonistically to the T2contrast.Summarizing, all types of multiple sclerosis

plaques were best or at least equally well dem-onstrated by the STIR-FSE sequence, whichholds true, in our experience, also for othertypes of intrinsic cord lesions occurring in pa-tients with a myelopathy. Particularly if doneafter the evaluation of extramedullary or extra-dural lesions with heavily T2-weighted FSE se-quences, STIR-FSE sequences might discloseadditional intrinsic cord abnormalities.

Conclusions

The FSE technique improves the overall im-age quality of T2-weighted images as com-pared with CSE images. This, however, doesnot necessarily improve the visibility of intrinsicspinal cord lesions, such as multiple sclerosisplaques. Short TEs and short echo trains seemto be advantageous for spinal cord imaging,whereas long TEs and long echo trains are ben-eficial for showing extramedullary and extra-dural disease. STIR-FSE appears to be the se-quence of choice for the assessment of spinalmultiple sclerosis plaques because it providesthe highest lesion contrast, which seems to beadvantageous for the assessment of patientswith a myelopathy. The FLAIR-FSE sequence isof minor diagnostic value for cervical multiplesclerosis plaques, owing to poor lesion contrastand cerebrospinal fluid pulsation artifacts.

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