Adam E. Flanders

Perfusion-CT Assessment of Infarct Core and Penumbra: Receiver Operating Characteristic Curve Analysis in 130 Patients Suspected of Acute Hemispheric Stroke

Background and Purpose— Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra. Methods— One hundred and thirty patients with symptoms suggesting hemispheric stroke ≤12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard. Results— The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml×100 g−1. Conclusion— In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.

Results of a Pilot Study Involving the Use of an Antisense Oligodeoxynucleotide Directed Against the Insulin-Like Growth Factor Type I Receptor in Malignant Astrocytomas

PURPOSE Preclinical animal experiments support the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor (IGF-IR/AS ODN) as an effective potential antitumor agent. We performed a human pilot safety and feasibility study using an IGF-IR/AS ODN strategy in patients with malignant astrocytoma. PATIENTS AND METHODS Autologous glioma cells collected at surgery were treated ex vivo with an IGF-IR/AS ODN, encapsulated in diffusion chambers, reimplanted in the rectus sheath within 24 hours of craniotomy, and retrieved after a 24-hour in situ incubation. Serial posttreatment assessments included clinical examination, laboratory studies, and magnetic resonance imaging scans. RESULTS Other than deep venous thrombosis noted in some patients, no other treatment-related side effects were observed. IGF-IR/AS ODN-treated cells, when retrieved and assessed, were < or = 2% intact by trypan blue exclusion, and none of the intact cells were viable in culture thereafter. Parallel Western blots disclosed IGF-IR downregulation to < or = 10% after ex vivo antisense treatment. At follow-up, clinical and radiographic improvements were observed in eight of 12 patients, including three cases of distal recurrence with unexpected spontaneous or postsurgical regression at either the primary or the distant intracranial site. CONCLUSION Ex vivo IGF-IR/AS ODN treatment of autologous glioma cells induces apoptosis and a host response in vivo without unusual side effects. Subsequent transient and sustained radiographic and clinical improvements warrant further clinical investigations.

Magnetic resonance evaluation of the intervertebral disc, spinal ligaments, and spinal cord before and after closed traction reduction of cervical spine dislocations.

STUDY DESIGN A prospective clinical study using magnetic resonance imaging of the cervical spine in a consecutive series of patients with cervical spine dislocations. OBJECTIVES To determine the incidence of intervertebral disc herniations and injury to the spinal ligaments before and after awake closed traction reduction of cervical spine dislocations. SUMMARY OF BACKGROUND DATA Prior series in which the prereduction imaging of disc herniations in the dislocated cervical spine are described have been anecdotal and have involved small numbers of patients. In addition, no uniform clinical criteria to define the presence of an intervertebral disc herniation in the dislocated cervical spine has been described. The incidence of disc herniations in the unreduced dislocated cervical spine is unknown. METHODS Eleven consecutive patients with cervical spine dislocations who met the clinical criteria for an awake closed traction reduction had prereduction and postreduction magnetic resonance imaging. Using strict clinical criteria for the definition of an intervertebral disc herniation, the presence or absence of disc herniation, spinal ligament injury, and cord injury was determined. Neurologic status before, during, and after the closed reduction maneuver was documented. RESULTS Disc herniations were identified in 2 of 11 patients before reduction. Awake closed traction reduction was successful in 9 of the 11 patients. Of the nine patients with a successful closed reduction, two had disc herniations before reduction, and five had disc herniations after reduction. No patient had neurologic worsening after attempted awake closed traction reduction. CONCLUSIONS The process of closed traction reduction appears to increase the incidence of intervertebral disc herniations. The relation of these findings, however, to the neurologic safety of awake closed traction reduction remain unclear.

Magnetic resonance imaging analysis of soft tissue disruption after flexion-distraction injuries of the subaxial cervical spine.

Study Design. A retrospective study was performed with the use of magnetic resonance imaging to evaluate the type and degree of soft tissue disruption associated with flexion-distraction injuries of the subaxial spine. Objective. To determine what soft tissue structures are injured in flexion-distraction injuries of the subaxial spine. Summary of Background Data. Prior published reports of unilateral and bilateral cervical facet dislocations have described the analyzed mechanisms and biomechanics of this injury subtype. No retrospective magnetic resonance imaging analysis of associated soft tissue disruption has been documented. Methods. Magnetic resonance imaging evaluations of the cervical spine were obtained for all patients with a flexion-distraction injury, Stages 2 (unilateral facet dislocation) and 3 (bilateral facet dislocation), between September 1994 and May 1998. Two neuroradiologists, blinded to both clinical and radiographic findings, graded all the soft tissue structures for evidence of attenuation or disruption. The soft tissue structures were graded on a scale of 1 (intact), 2 (indeterminate), or 3 (disrupted). Results. For this study, 48 patients satisfied the inclusion criteria: 25 with unilateral facet dislocation and 23 with bilateral facet dislocation. Disruption to the posterior musculature, interspinous ligament, supraspinous ligament, facet capsule, ligamentum flavum, and posterior and anterior longitudinal ligaments was found in a statistically significant number of patients with bilateral facet dislocation. For most of these structures, disruption was found to be statistically significant in patients with a unilateral facet dislocation, except for the posterior longitudinal ligament, in which significance was not consistently demonstrated using 95% confidence intervals in the binomial testing. In a comparison between unilateral and bilateral facet dislocations using a two-sided Fisher’s exact test, it was found that disruption to the anterior and posterior longitudinal ligaments and the left facet capsule were statistically significant, with all three more prominent in bilateral facet dislocation. A multivariate analysis between unilateral and bilateral facet dislocations showed that disruption to the anterior longitudinal ligament was associated significantly with a bilateral facet dislocation. Disc disruption was found to be associated significantly with both injury types, but was more common in bilateral facet dislocation, although this difference in intergroup comparisons was not statistically significant. Conclusions. Unilateral and bilateral facet dislocations of the subaxial spine are associated with damage to numerous soft tissue structures that provide stability to the lower cervical spine. Damage to the posterior longitudinal ligament did not occur consistently in unilateral facet dislocations. Bilateral facet dislocations were associated significantly with disruption to the posterior and anterior longitudinal ligaments and left facet capsule, as compared with unilateral facet dislocations. Magnetic resonance imaging allows visualization of these disruptions.

Neuroimaging in Traumatic Spinal Cord Injury: An Evidence-based Review for Clinical Practice and Research

Abstract Objective: To perform an evidence-based review of the literature on neuroimaging techniques utilized in spinal cord injury clinical practice and research. Methods: A search of the medical literature for articles on specific neuroimaging techniques used in SCI resulted in 2,302 published reports. Review at the abstract and full report level yielded 99 clinical and pre- clinical articles that were evaluated in detail. Sixty nine were clinical research studies subjected to quality of evidence grading. Twenty-three articles were drawn from the pre-clinical animal model literature and used for supportive evidence. Seven review articles were included to add an element of previous syntheses of current thinking on neuroimaging topics to the committee process (the review articles were not graded for quality of evidence). A list of clinical and research questions that might be answered on a variety of neuroimaging topics was created for use in article review. Recommendations on the use of neuroimaging in spinal cord injury treatment and research were made based on the quality of evidence. Results: Of the 69 original clinical research articles covering a range of neuroimaging questions, only one was judged to provide Class I evidence, 22 provided Class II evidence, 17 Class III evidence, and 29 Class IV evidence. Recommendations: MRI should be used as the imaging modality of choice for evaluation of the spinal cord after injury. CT and plain radiography should be used to assess the bony anatomy of the spine in patients with SCI. MRI may be used to identify the location of spinal cord injury. MRI may be used to demonstrate the degree of spinal cord compression after SCI. MRI findings of parenchymal hemorrhage/ contusion, edema, and spinal cord disruption in acute and subacute SCI may contribute to the understanding of severity of injury and prognosis for neurological improvement. MRI-Diffuslon Weighted Imaging may be useful in quantifying the extent of axonal loss after spinal cord injury. Functional MRI may be useful in measuring the anatomic functional/metabolic correlates of sensory-motor activities in persons with SCI. MR Spectroscopy may be used to measure the biochemical characteristics of the brain and spinal cord following SCI. Intraoperative Spinal Sonography may be used to identify spinal and spinal cord anatomy and gross pathology during surgical procedures. Further research in these areas is warranted to improve the strength of evidence supporting the use of neuroimaging modalities. Positron Emission Tomography may be used to assess metabolic activity of CNS tissue (brain and spinal cord) in patients with SCI.

Injury of the posterior ligamentous complex of the thoracolumbar spine: a prospective evaluation of the diagnostic accuracy of magnetic resonance imaging.

Study Design. Prospective diagnostic imaging study. Objective. To determine the accuracy of magnetic resonance imaging (MRI) in diagnosing injury of the posterior ligamentous complex (PLC) in patients with thoracolumbar trauma. Summary of Background Data. Treatment decisions in thoracolumbar injury patients are currently based on the status of the PLC. It is, therefore, important to understand the accuracy of MRI in diagnosing varying degrees of PLC injury. Prior studies report that MRI is up to 100% sensitive for diagnosing PCL injury. Methods. Patients with an acute injury from T1 to L3 who required posterior surgery were prospectively studied. A musculoskeletal radiologist, based on the preoperative MRI findings, characterized each of the 6 components of the PLC as intact, incompletely disrupted, or disrupted. During the surgical procedure, the surgeon identified each component of the PLC as intact, incompletely disrupted, or disrupted. The radiologists interpretation and surgical findings were compared. Results. Forty-two patients with 62 levels of injury were studied. There were 33 males (78.6%) and 9 females (21.4%), and the average age was 35.7 years. According to the kappa score, there was a moderate level of agreement between the radiologists interpretation and the intraoperative findings for all PLC components except the thoracolumbar fascia, for which there was slight agreement. The sensitivity for the various PLC components ranged from 79% (left facet capsule) to 90% (interspinous ligament). The specificity ranged from 53% (thoracolumbar fascia) to 65% (ligamentum flavum). There was less agreement between the radiologist and surgeon for the patients with less severe neurologic compromise, i.e., those patients with an AIS grade of either D or E. Conclusion. The sensitivity and specificity of MRI for diagnosing injury of the PLC are lower than previously reported in the literature. The integrity of the PLC as determined by MRI should not be used in isolation to determine treatment.

Tracing superior longitudinal fasciculus connectivity in the human brain using high resolution diffusion tensor tractography

The major language pathways such as superior longitudinal fasciculus (SLF) pathways have been outlined by experimental and diffusion tensor imaging (DTI) studies. The SLF I and some of the superior parietal lobule connections of the SLF pathways have not been depicted by prior DTI studies due to the lack of imaging sensitivity and adequate spatial resolution. In the current study, the trajectory of the SLF fibers has been delineated on five healthy human subjects using diffusion tensor tractography on a 3.0-T scanner at high spatial resolution. We also demonstrate for the first time the trajectory and connectivity of the SLF fibers in relation to other language pathways as well as the superior parietal lobule connections of the language circuit using high spatial resolution DTI in the healthy adult human brain.

Role of Magnetic Resonance Imaging in the Evaluation of the Hydroxyapatite Orbital Implant

The role of magnetic resonance imaging (MRI) in the assessment of fibrovascular ingrowth in the integrated hydroxyapatite orbital implant is evaluated. Fifteen patients who underwent enucleation and placement of a hydroxyapatite orbital implant were evaluated for degree of implant vascularity with gadolinium-DPTA-enhanced MRI with surface coil before drilling the implant. On T1-weighted images, the hydroxyapatite sphere appeared with intermediate signal. After gadolinium-DPTA administration, all patients showed an enhancement in the implant consistent with the presence of fibrovascular ingrowth. The enhancement was most notable in the peripheral portions of the sphere and was seen as early as 5 months after implantation. Comparison of gadolinium-DPTA-enhanced MRI with contrast-enhanced computed tomography, ultrasonography, and color Doppler imaging suggests that these latter techniques are not as helpful in the detection of the fibrovascular tissue in the orbital implant. Bone scan, a technique used by many surgeons, demonstrates fibrovascular ingrowth, but it is limited by its one-dimensional low-resolution image. Because of its three-dimensional capability and its highest resolution, contrast-enhanced MRI with surface coil appears to be the best imaging method for evaluating the hydroxyapatite orbital implant and its fibrovascular ingrowth.

Outcome Prediction in Patients with Glioblastoma by Using Imaging, Clinical, and Genomic Biomarkers: Focus on the Nonenhancing Component of the Tumor

PURPOSE To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. MATERIALS AND METHODS An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material-enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. RESULTS Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49-1.79 years). CONCLUSION Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features.

Failure of standard imaging to detect a cervical fracture in a patient with ankylosing spondylitis.

Study Design. Retrospective case study of 38-year-old male with ankylosing spondylitis who presented with a Brown-Séquard syndrome following a fall and an occult fracture on initial spinal imaging studies. Objective. To review the recommended imaging protocol in a patient with ankylosing spondylitis and a suspected cervical spine fracture. Summary of Background Data. Plain radiographic imaging using orthogonal views can detect the majority of spinal fractures. However, fracture identification is particularly difficult in patients with ankylosing spondylitis. Of the various contemporary imaging methods, [magnetic resonance imaging (MRI), computed tomography (CT), nuclear scanning] high-definition multidetector CT scanning is the most useful in identifying subtle fractures, but in metabolic bone diseases the utility of these methods is unknown. Methods. Retrospective radiographic evaluation of imaging studies of ankylosing spondylitis patient with occult fracture by five spine surgeons and neuroradiologists, followed with detailed review and interpretation of literature concerning present radiology techniques and methods to isolate occult fractures. Results. Initial imaging studies, including plain radiographs of the spinal axis, cervical and thoracic single-detector CT with reconstructed images, and MRI, were unremarkable in detecting an occult cervical spine fracture in a patient with ankylosing spondylitis and a spinal cord injury following a fall. The patient was placed empirically in a halo orthosis and a high definition multidetector CT scan was obtained. This study demonstrated a transverse fracture through the fused C6–C7 spinal level. Conclusion. Occult fractures in ankylosing spondylitis may not be apparent on routine plain radiographic and MRI studies. In the setting of ankylosing spondylitis, a high index of suspicion must be maintained in all patients presenting with spinal pain following even minor trauma. High-resolution multidetector CT imaging appears to be more sensitive and accurate in the diagnosis of fractures in this patient subgroup than other contemporary imaging methods.