Data from 20 patients (mean, 45.7 ⫾ 17.7 years of age; 2 women, 18 men) who were admitted to our trauma center following blunt force trauma with cervicalspine injuries and who were imaged by using MRimaging as part of a standard protocol were retrospectively compared with data from 8 healthy volunteers (mean, 34.2 ⫾ 10.7 years of age; 6 men, 2 women). Both groups were imaged by using conventional MRimaging and DTI. MRimaging studies were performed 2 hours to 15 days (mean, 32 ⫾ 22 hours) following injury. Indications for MRimaging studies in the trauma group included neurologic deficit on clinical examination localized to the cervicalspine (n ⫽ 16), assess- ment of the extent of ligamentous injury following cervicalspine frac- ture demonstrated on the admission CT of the cervicalspine (n ⫽ 2), and neck pain or tenderness unexplained by admission cervicalspine radiographs or CT examination (n ⫽ 2). Mechanisms of injury in- cluded motor vehicle collision (n ⫽ 7), motorcycle collision (n ⫽ 1), fall (n ⫽ 6), diving/surfing accident (n ⫽ 3), assault (n ⫽ 1), and all-terrain-vehicle crash (n ⫽ 1). The medical record was not available to determine the mechanism of injury in 1 patient. DTI data from 4 patients were not used for further analysis because of poor quality, Received April 9, 2007; accepted after revision November 4.
ported, a comprehensive study of the pediatric spinal cord that examines the accuracy and reproducibility of DTI measures has not yet been reported. The investigation of normative data of spinal cord DTI represents an additional important area of inquiry. The clinical significance of this study is 2-fold. First, as in any imaging study, a thorough understanding of the diffu- sion characteristics of the healthy spinal cord is essential for the clinical interpretation of images of the injured spinal cord. If DTI proves to be a feasible, accurate, and reliable method for quantifying diffusion changes in the pediatric spinal cord, it may be a useful neurodiagnostic supplement to conventional MRimaging. Second, normative DTI values will provide a basis for which to compare DTI values from children with spinal injuries, allowing for classification of the consequence of injury based on deviation from normal values. Therefore, the purpose of this study is to investigate DTI of the pediatric cervical spinal cord in healthy controls by 1) evaluating the
MRimaging scanning was performed on a 3T Trio scanner (Sie- mens, Erlangen, Germany). The scanning protocol included 2D sagittal T1 FLAIR, T2, STIR, axial T2, and 2-axial DTI acquisi- tions. For the current study, axial DTI and sagittal STIR sequences were used in processing and analysis, and thus, the parameters are listed. Axial DTI sequences are single-shot echo-planar acquisi- tions with reduced field of view in the anteroposterior dimension and 10 directions of diffusion, which were acquired during the same scan session with the following parameters: TR, 2600 ms; TE, 90 ms; 0.85 ⫻ 0.85 mm in-plane resolution; 200 mm ⫻ 100 mm field of view; section thickness, 5 mm; 0 intersection gap; 6 averages; bandwidth, 1766 Hz/pixel; and generalized autocali- brating partially parallel acquisition, 2. For each acquisition, im- ages were acquired with spherically distributed b-vectors at a b- value of 750 seconds/mm 2 , along with 6 interspersed minimally
NS079635 (statistical consulting). Mary Jane Mulcahey—RELATED: Grant: National Institute of Neurological Disorders and Stroke *; Support for Travel to Meetings for the Study or Other Purposes: National Institute of Neurological Disorders and Stroke *; UNRELATED: Board Membership: President, American Spinal Injury Asso- ciation, no payment; Vice President, Pediatric Spine Foundation, no payment; Con- sultancy: Topics in Spinal Cord Rehabilitation, Comments: Associate Editor; Grants/Grants Pending: Community Health Network Foundation,* Department of Defense,* Shriners Hospitals*; Royalties: Mac Keith Press (editor, book); Travel/ Accommodations/Meeting Expenses Unrelated to Activities Listed: Boston Reha- bilitation Outcomes Center (Visiting Scientist, 2015–2016). Feroze B. Mohamed— RELATED: Grant: National Institutes of Health–National Institute of Neurological Disorders and Stroke.* *Money paid to the institution.
brain tissue in healthy or diseased conditions, has provided useful information about regions with le- sions, such as edema and hemorrhage, following trau- matic brain injury. However, conventional MR imag- ing underestimates the extent of DAI, which may account for much of the transient clinical pathologic conditions following traumatic brain injury and per- haps for the residual neurologic and cognitive deficits that are associated with traumatic brain injury. In this study, we tested the hypothesis that a relatively new MRimaging technique, diffusiontensorimaging, could be more effective in identifying the effects of DAI in vivo. Images of FA and LI, as well as quantitative com- parison of the diffusion characteristics of selected groups of voxels, demonstrated significant differences of diffusion anisotropy between the two sides (left, right) of several white matter structures in the pa- tients. The same was not true in the neurologically normal control subjects. Therefore, regions with re- duced anisotropy, compared with their contralateral homologous regions, may be possible sites of DAI.
D iffusion MRimaging of the brain was first adopted for use in clinical neuroradiology during the early 1990s and was found to have immediate utility for the evaluation of sus- pected acute ischemic stroke. Since that time, enormous strides forward in the technology of diffusionimaging have greatly improved image quality and enabled many new clinical applications. These include the diagnosis of intracranial pyo- genic infections, masses, trauma, and vasogenic-versus-cyto- toxic edema. Furthermore, the advent of diffusiontensor im- aging (DTI) and fiber tractography has opened an entirely new noninvasive window on the white matter connectivity of the human brain. DTI and fiber tractography have already ad- vanced the scientific understanding of many neurologic and psychiatric disorders and have been applied clinically for the presurgical mapping of eloquent white matter tracts before intracranial mass resections.
DTI of the cervicalspine with region-of-interest analysis was suc- cessfully performed in all patients. In most cases, extensive degen- erative change resulted in multilevel CSM. All MRimaging mea- surements, except C7-T1 FA, were found to exhibit a normal distribution. However, no clinical score measurement fit a nor- mal distribution. As described below, agreement was found be- tween FA values from region-of-interest analysis of axial DTI data and baseline mJOA and Nurick scores. Of the 15 subjects who underwent surgery, a significant relationship was found between FA values and postoperative functional recovery assessed by NDI.
The present study revealed significant alteration in DTI met- rics in a group of patients with mTBI in several brain regions, and these changes were highly correlated with PCS severity and emotional distress. Detailed analyses of the diffusivities along different directions demonstrate the likelihood of cyto- toxic edema as the probable mechanism of injury in acute mTBI. Voxel-based DTI analysis is capable of identifying po- tentially diffuse axonal injury-vulnerable regions invisible to CT and conventional MRimaging, which may assist in classi- fication, early diagnosis, and treatment.
Whole Cord Diffusion Characteristics. FA and diffusion charac- teristics were analyzed for all subjects and all vertebral levels to deter- mine if global changes in diffusivity occur along the neuraxis during the chronic stages of SCI. Tests for normality (Kolmogorov-Smirnov test) were performed before analysis to ensure that parametric statis- tics were applicable. If data were normally distributed (P ⬎ .05), a 2-way analysis of variance (ANOVA) with pooled variance (fixed fac- tors: injury group [injured/uninjured], vertebral level; random factor: subject) was performed to compare injured subjects with uninjured subjects. In addition, a univariate general linear model (GLM; fixed factors: vertebral level, completeness of injury [complete/incom- plete], injury level [thoracic/cervical], vertebral level ⫻ injury level, vertebral level ⫻ completeness of injury; random factor: subject) was performed to examine differences between injured subject groups. The Tukey test for multiple comparisons was performed for post hoc comparisons. All tests had a significance level of ␣ ⫽ .05.
ring in a fibrillary organized tissue (e.g. the brain) . Fractional anisotropy (FA) and mean diffusivity are sca- lars that describe the asymmetry of such diffusion; the asymmetry is due to the barriers of the myelin sheet of the axons and cell membranes . DTI images are coded with respect to the FA, the diffusivity (ADC), or the predominant direction of the tensor . From these maps, it is possible to perform 3D-reconstructions of brain white matter using MR tractography (MRT)  . The localization of white matter tracts in the brain has been demonstrated as an important factor affecting pre-surgical planning, counseling, and outcome -. In addi- tion DTI is important in traumatic brain injury as an outcome surrogate  . Therefore, there is mounting evidence of the added clinical value of diffusiontensorimaging and MR tractography in these patient popula- tions . However, this study requires additional sequences and rigorous imaging post processing hence, in- curring additional scanning time and use of personnel resources. However, to our knowledge, no rigorous cost analysis of DTI and MR tractography has been done to determine the exact resources used and its exact cost, though some attempts have been made to characterize value -. The purpose of our study, therefore, was to determine the total direct costs (fixed and variable costs) of DTI and MR tractography .
discriminate between ADEM and MS. However, at present, no better clinical criteria for diagnosing ADEM are available (3, 4). We also selected our patients retrospectively, and this approach might have influenced our results. However, we think this is a minor issue in the present study for two reasons. First, we extensively reviewed all cases in which a diagnosis of ADEM would have been possible by using a pre- defined set of criteria. Second, at present and with whatever criteria, a diagnosis of ADEM can be made only after the onset of the symptoms (5, 8) when an alternative diagnosis of MS can be reasonably ex- cluded. In the present study, we also did not assess normal-appearing brain tissue and cervical cord changes in patients with ADEM at presentation. Therefore, we can not definitively rule out that re- versible changes can occur in the CNS normal-ap- pearing tissue in the acute phase of ADEM, when a differential diagnosis with MS is more compelling. Sublethal axonal injury can occur in the normal-ap- pearing tissue distant from lesions that are visible on T2-weighted images obtained in patients with MS, and they can cause MR spectroscopic changes (38). As a consequence, similar changes arguably can occur in patients with ADEM at presentation. Nevertheless, although quantitative MR studies of the normal-ap- pearing brain tissue and cord tissue in patients with ADEM at presentation are warranted to clarify this issue, sublethal axonal injury is unlikely to cause mod- ifications in the relative proportions of intra- and extacellular water and in the size of water-filled spaces that are large enough to cause MTR and D changes comparable to those seen in MS (10–12, 14, 15, 24).
This was a Health Insurance Portability and Accountability Act– compliant descriptive retrospective study performed after ap- proval from the institutional review board at a pediatric tertiary referral center. Using the center’s trauma registry, a query was generated to provide a study data base including all children younger than 5 years of age who presented with NAT from July 2004 through September 2012. The trauma registry is a disease- specific data collection composed of a file of uniform data ele- ments designed to capture data. From the generated query results, charts were evaluated thoroughly to determine study eligibility. Children with spinal injuries resulting from mechanisms other than NAT were not included. Only the patients in whom NAT had been documented by the child abuse team were included in the study data base. The presence of AHT was not a requirement for inclusion, but the diagnosis of NAT was. The discharge status was evaluated to identify mortality related to NAT in this cohort.
Limitations of this study include small sample size and lim- ited surgical visualization as discussed above. The issue of uti- lizing surgical findings as the reference standard is not without limitations; however, this approach provides a ready compar- ison that is directly suited to our goal of determining how MRimaging might potentially affect surgical decision making, in addition to providing an external anatomic standard that is lacking in most other studies on this subject. We suspect that the exquisite soft tissue contrast afforded by MRimaging picks up subtle ligamentous sprains and soft tissue contusions. Such findings may not be appreciated at surgery if there is no frank structural disruption. Nevertheless, soft tissue con- tusion without disruption seen on MRimaging is important in that it may falsely suggest disruptive injury and potential sur- gical instability. Whether clinical decisions based on this limited accuracy are of consequence should be evaluated prospectively.
skeletal muscle contractions. Taller patients would be more likely to be affected due to the longer length of their peripheral nerves. All clinical MRimaging scanners meet FDA safety guidelines for dB/dt limits. The current generation of MR im- agers with 40 – 80 mT/m maximal gradient amplitude and 150 –200 mT/m per millisecond maximal slew rate enables DWI with better anatomic fidelity than older MRimaging systems. Some newer MRimaging scanners are equipped with even stronger and faster gradients that have a reduced FOV, to stay within dB/dt guidelines, and are suitable for head imaging but not for spine or body imaging. Besides maximal amplitude and slew rate, another important factor is the gradient duty cycle, which can be limited by heating constraints. Larger duty cycles permit more 2D diffusion-weighted sections to be ac- quired in a given TR. Modern MRimaging systems have wa- ter-cooled gradients with larger duty cycles than older sys- tems, which allow faster DWI.
The results of voxel-wise analysis cannot not be regarded as a strict superset of the results from ROI-based analysis, and, thus, these approaches at times yield apparently contradictory results. For example, although the ROI-based analyses found group differences in FA values in the ALIC and PLIC, the voxel-wise analyses revealed group differences in only a small region in PLIC and no differences in ALIC (Fig 2). There are several possible sources of these apparent discrepancies. First, the use of very stringent criteria to control for multiple com- parisons in the voxel-wise analyses will limit the number of voxels that reach the significant threshold. A more liberal stan- dard would lead to more voxels showing up as significant re- gions on Fig 2; however, there would be an accompanying increase in false-positive results, which might be misleading. The normalization procedure used in the voxel-wise analysis might serve as another potential source of discrepancy. Nor- malizing data to a standard brain template is a routine proce- dure and has been applied extensively in various imaging stud- ies. 28,33 However, this approach involves approximation based
and is observed in patients with agenesis of the corpus callo- sum. In patients with this condition, during development of axonal fibers (future callosal fibers), the fibers are incapable of crossing the midline due to the absence of the massa commis- suralis, and nerve fibers instead follow a caudal course, grouped in a thick longitudinal Probst bundle. Diffusion ten- sor methods are most suitable for demonstrating it, and many articles on this bundle have been published describing results of diffusiontensor tractography. 19-24 Vachha et al 19 described other aberrant fibers in patients with myelomeningocele and Chiari II malformation. They described limbic fiber abnor- malities and noted that many patients had defects within the fornices and/or cingulum and that some had aberrant fibers of the cingulum. FT reconstruction images showed fibers of the cingulum crossing obliquely over the corpus callosum and cingulum, which appeared to be composed of multiple parallel aberrant bundles. 19 In other anomalies, such as holoprosen- cephaly and lissencephaly, abnormal fibers can also be dem- onstrated by using diffusiontensor methods. 21,23 However,
All MRimaging data were obtained by using a Signa LX 1.5-T clinical imager (GE Medical Systems, Milwaukee, WI). The machine was equipped with a self-shielding gradient set (23 mT/m maximum gradient strength, 120 T/m/s slew rate, and a horizontal bore with a 60-cm inner diameter) and manufac- turer-supplied birdcage quadrature head coil. Each patient underwent an MRimaging examination that consisted of a fast spin-echoT2-weighted sequence, the DT-MRimaging protocol described next, and a contrast material–enhanced T1-weighted volume sequence. After the DT-MRimaging protocol was completed, 20 mL of gadopentetate dimeglumine (Magnevist, Berlex Laboratories, Wayne, NJ) was administered intrave- nously. Parameters for the contrast-enhanced T1-weighted vol- ume sequence were a TR/TE/TI/NEX of 7.3/3.2/400/1, a field of view of 240 ⫻ 240 mm, an acquisition matrix of 256 ⫻ 256, and 110 contiguous axial sections of 1.5 mm thickness. The acquisition times were approximately 2 minutes for the fast spin-echo T2-weighted sequence, 15 minutes for the DT-MRimaging protocol, and 7 minutes for the T1-weighted volume sequence. Thus, the duration of the entire examination was approximately 30 minutes for each patient.
The assumptions and technical limitations of this study include the following: 1) gaussian diffusion of water in the brain and resultant tensor matrix symmetry (this assumption helps improve the ef- ficiency of diffusiontensorMRimaging for clinical purposes by allowing the complete characterization of the diffusiontensor using only six of the nine scalar elements; 2) suboptimal spatial separation of the diffusion-sensitizing gradients, which can neg- atively influence noise levels of the calculated ADC i , eigenvalues, and FA (36); 3) inability to
abnormal cortical gyral patterns consisting of regions of microgyria (primarily in frontal and perisylvian cortex) and regions with thickened pachygyric cortex (primarily perirolandic and occipital) are common (1, 2). Barkovich and Peck (1) described an association with germinolytic cysts. NALD shows usually heterotopia, pachygyria, polymicrogyria, and diffuse demyelination (2). IRD may have normal MRimaging findings (2). Three patients with PBD in another study had an un- usually late-onset white matter disease (5). On conven- tional MR images, cerebral demyelination with relative sparing of subcortical fibers and pronounced central cerebellar demyelination was shown (5).
One patients with SLE and 1 with NPSLE were excluded due to imaging artifacts. There was no significant differ- ence in age among all cohorts and no difference in disease duration, total cu- mulative prednisolone use (from dis- ease onset until the time of study), and the prevalence of radiologic abnor- malities of patients with NPSLE com- pared with those with SLE. All demo- graphics, radiologic abnormalities, prevalence of various neuropsychiat- ric symptoms, and P values of group comparisons are shown in Table 1.