
 neuromyelitis optica ( nmo ) has been traditionally considered a predominantly opticospinal disorder , but recent studies have shown that clinical spectrum of nmo includes cerebral and brainstem syndromes as well [ 13 ] .
brain lesions on magnetic resonance imaging ( mri ) are found in the majority of nmo patients with long - standing disease [ 1 , 2 , 46 ] , which makes it sometimes difficult to differentiate this disorder from multiple sclerosis ( ms ) .
ultrahigh - field mri ( 4 tesla or above ) affords an unprecedented view of brain structures and pathology in vivo on a submillimeter scale due to high signal - to - noise ratio [ 7 , 8 ] .
the largely enhanced susceptibility of ultrahigh - field mr effect provides unique contrast between lesions and veins .
this feature makes ultrahigh - field mr a valuable tool for differentiating plaques of ms , which frequently contain a venule , from lesions of other etiologies that rarely do .
our aim in this work is to characterize brain lesions in patients with neuromyelitis optica spectrum disorders ( nmosd ) using 7  t mr and to discuss the findings in the context of the growing literature on ultrahigh - field imaging in ms [ 919 ] .

 inclusion criteria in the study were the diagnosis of nmo - spectrum disorders ( nmosd ) defined either as nmo by 2006 wingerchuk et al .
criteria , or recurrent longitudinally extensive transverse myelitis ( letm ) with nmo igg seropositivity , or recurrent optic neuritis ( on ) with nmo igg seropositivity .
nmo igg was measured at the mayo clinic laboratory ( rochester , mn ) by either immunohistochemical or enzyme - linked immunosorbent assay .
all nonbedbound nmosd patients followed by the neurologists of the nyu - ms center ( i. k. and j. h. ) were invited to participate in the study . for each patient , we collected the following information : gender , ethnicity , country of birth , age at symptom onset , disease duration at mri , index event , number of optic neuritis and of transverse myelitis relapses , visual acuity and ambulatory status at last followup , nmosd therapy , and presence and number of vascular risk factors ( defined as history of smoking , hypertension , hypercholesterolemia , or cardiovascular disease ) .  
ultrahigh - field imaging was carried out on a 7-tesla whole - body human mr system ( magnetom , siemens medical solution , erlangen , germany ) at the center for biomedical imaging / radiology at nyu langone medical center , which uses gradients of 45  mt / m with maximum gradient strength of 72  mt / m effective and a slew rate of 200  t / m / s ( 346  t / m / s effective ) .
the head coil was used with a birdcage - like circularly polarized transmit coil and a 24-element phased array coil located on a close - fitting helmet - like device ( nova medical , inc . , ma ) . the imaging protocol consisted of high - resolution axial 2d high - resolution t2
* -weighted gradient echo ( gre ) , t2-weighted turbo spin - echo ( tse ) , fluid - attenuated inversion recovery ( flair ) , and sagittal t1-weighted 3d magnetization - prepared rapid acquisition of gradient - echo ( mprage ) imaging .
the parameters of t2 * -weighted gradient echo ( gre ) include tr / te / flip angle = 580  ms/25  ms/35 and slice thickness = 2  mm , with slice gap of 2.6  mm with pixel of 0.23  0.23  mm , which were optimized for better signal - to - noise and contrast between lesions and venous structures . for axial t2-weighted tse , the acquisition parameters were tr / te / flip angle = 14300/73  ms/144 ; slice thickness = 2  mm ; fov = 200  187  mm ; matrix = 384  384  mm . for axial space flair imaging , the acquisition parameters were tr / te / ti = 8000/380/2100  ms ; voxel size = 1  1  1  mm isotropic . for sagittal
t1-weighted 3d mprage , the acquisition parameters were tr / te / ti = 2250/2.37/1100  ms , section thickness = 1  mm ; fov = 256  256  mm , matrix = 384  384 .
infratentorial volume could not be reliably evaluated because our 7  t receive coil yielded poor signal - to - noise ratio in this region , and the examination was therefore limited to supratentorial region .
two experienced observers ( y. g. and i. k. ) examined t2-weighted and 2d gradient echo ( t2 * ) imaging sequences for presence of lesions . to reduce the possibility of misidentification , only the lesions that were present on both sequences were counted . for each lesion , we recorded lesion size , configuration , location , and presence or absence of central venule and of hypointense peripheral ring on t2 * sequence
. lesion localization was defined as periventricular ( < 2  mm of ventricular border ) , juxtacortical ( < 2  mm from cortical ribbon ) , subcortical / deep white matter ( > 2  mm from cortex or ventricle , excluding corpus callosum ) , corpus callosum , cortex , and deep grey matter nuclei .
lesions were described as  perivenous  if they were seen to be traversed by a vein on t2 * sequence .
data collection was carried out according to protocol approved by the institutional review boards of nyu - langone medical center , and all patients gave informed consent in writing before participation .
ten patients agreed to participate in the study , six of whom were diagnosed with nmo   and four with limited forms of nmo .
demographic , disease - related , and radiologic characteristics of our nmosd cohort are shown in table 1 .  
the total number of lesions was 92 ( mean number was 9.2  8.8 ; median : 6 ; range : 230 ) .
seventy - six lesions ( 83% ) were subcortical , 8 ( 9% ) were juxtacortical , 3 lesions ( 3% ) were found in corpus callosum , and 5 ( 5% ) were periventricular ( 4 of which were adjacent to frontal horns of the lateral ventricles ) .
all but three of the 92 lesions were <3  mm in cross - sectional diameter , and all lesions were < 5  mm .
the lesions generally appeared round on axial cross - sections ( figures 1(a)1(f ) ) .
thread - like  lesions , and these were invariably hypointense on t1-weighted sequences ( figures 2(a)2(d ) ) .
several lesions , which were <3  mm in cross - sectional diameter , could be seen on three consecutive slices , indicating that they were at least 6  mm long . in all , eight lesions ( 9% ) were classified as
 two patients had diffuse periependymal abnormalities on t2-weighted sequences ( figures 3(a ) and 3(b ) ) .
three perivenous lesions were seen in one patient with nmo who had a total of four lesions , and five patients had one perivenous lesion each .  
the group with limited form of nmosd , comprised of 4 patients , tended to have more lesions ( mean : 13.4 ) , compared to the six - patient nmo group ( mean : 4.8 ) , but the difference was not statistically significant ( mann - whitney u test , u = 16.5  p - two tailed = 0.35 ) .
we did not observe a trend for increasing lesion number with age , disease duration , or the number of vascular risk factors ( table 1 ) .
t2-weighted hyperintense lesions on 7  t mri were observed in all ten nmosd patients in our cohort .
nearly all lesions were round ( figure 1 ) , but several lesions had a distinct ,  thread - like  appearance on axial cross - section ( figure 2 ) .
we consider it unlikely that  thread - like  lesions represent dilated virchow - robin spaces ( vrs ) because of their location , orientation , and signal characteristics .
vrs are typically found in basal ganglia with penetrating arteries mostly from circle of willis .
they appear as round dots on axial plane with similar signal as csf ( i.e. , brightly hyperintense spots on t2-weighted sequence ) .
in contrast ,  thread - like  lesions found in our nmo patients were observed mostly in juxtacortical white matter and corpus callosum , do not follow arterial course , and were not as bright as csf on t2-weighted sequence .
thread - like lesion appearance has not , to our knowledge , been reported in other conditions , including ms , which is characterized by perivenous ovoid lesions .
with respect to lesion distribution , the overwhelming majority of lesions in nmosd ( ~85% ) were subcortical .
the few discrete periventricular lesions were mostly located anterior to the frontal horns ( figure 1(d ) ) and were more extensive than the typical 
two of our patients exhibited diffuse periventricular abnormalities ( figure 3 ) , which is notable in view of known rich expression of aquaporin-4 , the target of nmo igg , in the ependymal layer . in one patient
( figure 3(a ) ) , splenium of the corpus callosum was affected in the  diffuse spreading 
the discrepancy in the prevalences of diffuse spreading lesions in corpus callosum in our series ( 10% ) and the japanese series ( 71% ) could perhaps be due to lesser degree of disability of our cohort , in which only 30% of patients required any kind of ambulatory assistance compared to the japanese cohort , in which half of the patients needed ambulatory assistance .
a patient from the far east appears to manifest brain symptoms and large  nmo - specific  brain lesions more commonly than in the west [ 1 , 2 , 5 ] .
cortical lesions were not found in any of our patients in agreement with the recent radiographic studies that utilized double inversion recovery sequence   and ultrahigh - field mr   to image the cortex in nmo as well as a histopathologic study .
absence of focal cortical lesions in nmosd need not imply absence of other cortical pathology , but is helpful for differentiating nmo from ms , in which cortical lesions are increasingly recognized , especially with ultrahigh - field mr [ 1114 ] .  
importantly , only 9% of nmosd brain lesions in our series contained a central vessel .
this is in stark contrast with ms , in which 6080% of cerebral lesions visualized with ultrahigh - field mri are traversed by a venule [ 9 , 10 , 15 , 16 ] .
paucity of intralesional venules in our series is not contradictory to results of a study in which venules were detected in a high proportion of white matter lesions of any etiology on susceptibility weighted imaging .
the latter study focused exclusively on lesions > 3  mm in diameter , while nearly all lesions in our series were 3  mm in diameter .  
absent histopathological correlation , it is impossible to be certain that brain lesions seen in our cohort are due to an nmo - specific pathogenic process . some of the lesions could theoretically represent stigmata of  small vessel disease 
( svd ) , in itself a pathologically heterogeneous entity . for a number of reasons , svd origin of observed lesions seems to us to be less likely explanation .
first , the finding of juxtacortical and corpus callosum lesions and the absence of basal ganglia lesions militate against svd etiology .
secondly ,  thread - like lesions  ( figures 2(a)2(d ) ) have not been described in svd .
third , we could find no correlation between vascular risk factors and the number of brain lesions ( table 1 ) and observed small lesions in patients in their 20s and 30s with no vascular risk factors .
lastly , in at least three of our patients , a lesion on 7  t mri was seen to enhance with gadolinium previously on a conventional mri study ( unpublished data ) .
whatever the pathogenesis of small subcortical lesions nmo may be , these  non - specific  lesions represent the most consistent feature of nmo on brain mri .  
our data is broadly consistent with recently published findings of 7  t mri of the brain in 10 german nmosd patients .
the german nmosd cohort was somewhat older than ours ( 46 years versus 42 in our group ) but had a slightly shorter disease duration ( 7 years versus 9 years ) .
both groups were exclusively female , and all but one patient were nmo igg seropositive . in neither ours nor the german nmosd cohort were any cortical lesions observed , and the lesions that were present were predominantly small and subcortical
the proportion of perivenous lesions among the german nmosd patients was higher than in our group ( 35% versus 9% ) , which may be related to the higher average number of lesions in their cohort ( 14 lesions versus 9 lesions in our group ) .
importantly , in both cohorts , the number of perivenous lesions was significantly smaller than what is typically reported in ms ( > 80% ) .
finally , although hypointense ring , which is indicative of iron or hemosiderin deposition , is found in a significant minority of ms lesions [ 17 , 28 ] , it was only observed in one out of ten nmosd patients in the german nmo cohort and none of our ten patients .
this further supports differential brain lesion pathogenesis in ms and nmo .   our work and that of sinnecker et al .  
demonstrate that small round subcortical lesion without a central venule or hypointense ring is the most characteristic feature on nmosd on ultrahigh - field mri .
in contrast , the signature lesion of ms is oblong , periventricular , and traversed centrally by a venule [ 9 , 10 , 15 , 16 ] , corresponding to  dawson 's fingers  , described pathologically almost a hundred years ago .
dawson 's fingers  and cortical lesions on 7  t mri in a patient with multiple , > 9 , t2 hyperintense lesions should alert the radiologist that diagnosis of ms is unlikely .  
ultrahigh - field imaging of brain in nmosd provides strong supportive evidence that ms and nmo constitute two distinct nosological entities despite their predilection for the same organs .
 
 background . 
 brain lesions are common in neuromyelitis optica spectrum disorder ( nmosd ) and may resemble lesions of multiple sclerosis ( ms ) . objectives . to describe the imaging characteristics of supratentorial lesions in nmosd on ultrahigh - field ( 7  t ) mri with special attention to vessel - lesion relationship . 
 methods . 
 ten nmosd patients , all women and all seropositive for nmo igg , with mean age of 51.3  15.4 years and disease duration of 9.2  6.4 years , were scanned at a 7  t whole - body human mr system with high - resolution 2d gradient echo sequence optimized to best visualize lesions and venous structures , t2- and t1-weighted imaging . results . in 10 patients with nmosd , 
 a total of 92 lesions were observed ( mean : 9.2  8.8 ; range : 230 ) , but only 8 lesions ( 9% ) were traversed by a central venule . 
 all lesions were < 5  mm in diameter , and 83% were located in subcortical white matter . there were no lesions in the cortex or basal ganglia . 
 two patients exhibited diffuse periependymal abnormalities on flair . 
 conclusions . 
 small , subcortical lesions without a central venule are the most consistent finding of nmosd on 7  t mri of the brain . 
 ultrahigh - field imaging may be useful for differentiating between nmosd and ms . 
1. Introduction
2. Methods
3. Results
4. Discussion