Longitudinal evaluation of diffusion tensor imaging and cognition in systemic lupus erythematosus.

Objective This pilot study aimed to examine longitudinal changes in brain structure and function in patients with systemic lupus erythematosus (SLE) using diffusion tensor imaging (DTI) and neuropsychological testing. Methods Fifteen female SLE patients with no history of major neuropsychiatric (NP) manifestations had brain magnetic resonance imaging (MRI) with DTI at baseline and approximately 1.5 years later. At the same time points, a standardized battery of cognitive tests yielding a global cognitive impairment index (CII) was administered. At baseline, the SLE patients had mean age of 34.0 years (SD = 11.4), mean education of 14.9 years (SD = 2.1), and mean disease duration of 121.5 months (SD = 106.5). The MRI images were acquired with a 3T GE MRI scanner. A DTI sequence with 33 diffusion directions and b-value of 800 s/mm2 was used. Image acquisition time was about 10 minutes. Results No significant change in cognitive dysfunction (from the CII) was detected. Clinically evaluated MRI scans remained essentially unchanged, with 62% considered normal at both times, and the remainder showing white matter (WM) hyperintensities that remained stable or resolved. DTI showed decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in bilateral cerebral WM and gray matter (GM) with no major change in NP status, medical symptoms, or medications over time. Lower FA was found in the following regions: left and right cerebral WM, and in GM areas including the parahippocampal gyrus, thalamus, precentral gyrus, postcentral gyrus, angular gyrus, parietal lobe, and cerebellum. Greater MD was found in the following regions: left and right cerebral WM, frontal cortex, left cerebral cortex, and the putamen. Conclusions This is the first longitudinal study of DTI and cognition in SLE, and results disclosed changes in both WM and GM without cognitive decline over an 18-month period. DTI abnormalities in our participants were not associated with emergent NP activity, medical decline, or medication changes, and the microstructural changes developed in the absence of macrostructural abnormalities on standard MRI. Microstructural changes may relate to ongoing inflammation, and the stability of cognitive function may be explained by medical treatment, the variability of NP progression in SLE, or the impact of cognitive reserve.

Protrusion of the Infraorbital Nerve into the Maxillary Sinus on CT: Prevalence, Proposed Grading Method, and Suggested Clinical Implications.

BACKGROUND AND PURPOSE: The infraorbital nerve arises from the maxillary branch of the trigeminal nerve and normally traverses the orbital floor in the infraorbital canal. Sometimes, however, the infraorbital canal protrudes into the maxillary sinus separate from the orbital floor. We systematically studied the prevalence of this variant. MATERIALS AND METHODS: We performed a retrospective review of 500 consecutive sinus CTs performed at our outpatient centers. The infraorbital nerve protruded into the maxillary sinus if the entire wall of the infraorbital canal was separate from the walls of the sinus. We recorded the length of the bony septum that attached the infraorbital canal to the wall of the maxillary sinus and noted whether the protrusion was bilateral. We also measured the distance from the inferior orbital rim where the infraorbital canal begins to protrude into the sinus. RESULTS: There was a prevalence of 10.8% for infraorbital canal protrusion into the maxillary sinus and 5.6% for bilateral protrusion. The median length of the bony septum attaching the infraorbital canal to a maxillary sinus wall, which was invariably present, was 4 mm. The median distance at which the infraorbital nerve began to protrude into the sinus was 11 mm posterior to the inferior orbital rim. CONCLUSIONS: Although this condition has been reported in only 3 patients previously, infraorbital canal protrusion into the maxillary sinus was present in >10% of our cohort. Identification of this variant on CT could help a surgeon avoid patient injury.

Evaluating CT perfusion using outcome measures of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH and remains a leading cause of morbidity and mortality. Our aim was to evaluate CTP in aneurysmal SAH by using outcome measures of DCI. MATERIALS AND METHODS: This was a retrospective study of consecutive patients with SAH enrolled in a prospective institutional review board-approved clinical accuracy trial. Qualitative CTP deficits were determined by 2 neuroradiologists blinded to clinical and imaging data. Quantitative CTP was performed by using a standardized protocol with region-of-interest placement sampling of the cortex. Primary outcome measures were permanent neurologic deficits and infarction. The secondary outcome measure was DCI, defined as clinical deterioration. CTP test characteristics (95% CI) were determined for each outcome measure. Statistical significance was calculated by using the Fisher exact and Student t tests. ROC curves were generated to determine accuracy and threshold analysis. RESULTS: Ninety-six patients were included. Permanent neurologic deficits developed in 33% (32/96). CTP deficits were seen in 78% (25/32) of those who developed permanent neurologic deficits and 34% (22/64) of those without (P < .0001). CTP deficits had 78% (61%-89%) sensitivity, 66% (53%-76%) specificity, and 53% (39%-67%) positive and 86% (73%-93%) negative predictive values. Infarction occurred in 18% (17/96). CTP deficits were seen in 88% (15/17) of those who developed infarction and 41% (32/79) of those without (P = .0004). CTP deficits had an 88% (66%-97%) sensitivity, 59% (48%-70%) specificity, and 32% (20%-46%) positive and 96% (86%-99%) negative predictive values. DCI was diagnosed in 50% (48/96). CTP deficits were seen in 81% (39/48) of patients with DCI and in 17% (8/48) of those without (P < .0001). CTP deficits had 81% (68%-90%) sensitivity, 83% (70%-91%) specificity, and 83% (70%-91%) positive and 82% (69%-90%) negative predictive values. Quantitative CTP revealed significantly reduced CBF and prolonged MTT for DCI, permanent neurologic deficits, and infarction. ROC analysis showed that CBF and MTT had the highest accuracy. CONCLUSIONS: CTP may add prognostic information regarding DCI and poor outcomes in aneurysmal SAH.

Using quantitative CT perfusion for evaluation of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH leading to permanent neurologic deficits, infarction, and death. Our aim was to prospectively evaluate the diagnostic accuracy of CTP and to determine a quantitative threshold for DCI in aneurysmal SAH. MATERIALS AND METHODS: Patients with SAH were prospectively enrolled in a protocol approved by the institutional review board. CTP was performed during the typical time period for DCI, between days 6 and 8 following SAH. Quantitative CBF, CBV, and MTT values were obtained by using standard region-of-interest placement sampling of gray matter. The reference standard for DCI is controversial and consisted of clinical and imaging criteria in this study. In a subanalysis of vasospasm, DSA was used as the reference standard. ROC curves determined the diagnostic accuracy by using AUC. Optimal threshold values were calculated by using the patient population utility method. RESULTS: Ninety-seven patients were included; 41% (40/97) had DCI. Overall diagnostic accuracy was 93% for CBF, 88% for MTT, and 72% for CBV. Optimal threshold values were 35 mL/100 g/min (90% sensitivity, 68% specificity) for CBF and 5.5 seconds (73% sensitivity, 79% specificity) for MTT. In the subanalysis (n = 57), 63% (36/57) had vasospasm. Overall diagnostic accuracy was 94% for CBF, 85% for MTT, and 72% for CBV. Optimal threshold values were 36.5 mL/100 g/min (95% sensitivity, 70% specificity) for CBF and 5.4 seconds (78% sensitivity, 70% specificity) for MTT. CONCLUSIONS: CBF and MTT have the highest overall diagnostic accuracy. Threshold values of 35 mL/100 g/min for CBF and 5.5-second MTT are suggested for DCI on the basis of the patient population utility method. Absolute threshold values may not be generalizable due to differences in scanner equipment and postprocessing methods.

Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) may be a useful index of microstructural changes implicated in diffuse axonal injury (DAI) linked to persistent postconcussive symptoms, especially in mild traumatic brain injury (TBI), for which conventional MR imaging techniques may lack sensitivity. We hypothesized that for mild TBI, DTI measures of DAI would correlate with impairments in reaction time, whereas the number of focal lesions on conventional 3T MR imaging would not. MATERIALS AND METHODS: Thirty-four adult patients with mild TBI with persistent symptoms were assessed for DAI by quantifying traumatic microhemorrhages detected on a conventional set of T2*-weighted gradient-echo images and by DTI measures of fractional anisotropy (FA) within a set of a priori regions of interest. FA values 2.5 SDs below the region average, based on a group of 26 healthy control adults, were coded as exhibiting DAI. RESULTS: DTI measures revealed several predominant regions of damage including the anterior corona radiata (41% of the patients), uncinate fasciculus (29%), genu of the corpus callosum (21%), inferior longitudinal fasciculus (21%), and cingulum bundle (18%). The number of damaged white matter structures as quantified by DTI was significantly correlated with mean reaction time on a simple cognitive task (r = 0.49, P = .012). In contradistinction, the number of traumatic microhemorrhages was uncorrelated with reaction time (r = -0.08, P = .71). CONCLUSION: Microstructural white matter lesions detected by DTI correlate with persistent cognitive deficits in mild TBI, even in populations in which conventional measures do not. DTI measures may thus contribute additional diagnostic information related to DAI.

Reassessment: neuroimaging in the emergency patient presenting with seizure (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To reassess the value of neuroimaging of the emergency patient presenting with seizure as a screening procedure for providing information that will change acute management, and to reassess clinical and historical features associated with an abnormal neuroimaging study in these patients. METHODS: A broad-based panel with topic expertise evaluated the available evidence based on a structured literature review using a Medline search from 1966 until November 2004. RESULTS: The 15 articles meeting criteria were Class II or III evidence since interpretation was not masked to the patient's clinical presentation; most were series including 22 to 875 patients. There is evidence that for adults with first seizure, cranial CT will change acute management in 9 to 17% of patients. CT in the emergency department for children presenting with first seizure will change acute management in approximately 3 to 8%. There is no clear difference between rates of abnormal emergent CT for patients with chronic seizures vs first. Children <6 months presenting with seizures have clinically relevant abnormalities on CT scans 50% of the time. Persons with AIDS and first seizure have high rates of abnormalities, and CNS toxoplasmosis is frequently found. Abnormal neurologic examination, predisposing history, or focal seizure onset are probably predictive of an abnormal CT study in this context. CONCLUSIONS: Immediate noncontrast CT is possibly useful for emergency patients presenting with seizure to guide appropriate acute management especially where there is an abnormal neurologic examination, predisposing history, or focal seizure onset.

Effect of training and experience on qualitative and quantitative CT perfusion data.

BACKGROUND AND PURPOSE: To evaluate interobserver reliability of obtaining CT perfusion (CTP) data for qualitative identification of perfusion abnormality and quantitative assessment through regions-of-interest (ROIs) placement. MATERIALS AND METHODS: Six observers participated in the study (neuroradiology attending physician, neurology attending physician, neuroradiology fellow, radiology resident physician, senior and junior CT technologists). After a brief training session, each observer evaluated 20 CTP datasets for qualitative identification of a right- or left-sided perfusion abnormality or symmetric perfusion. Observers also placed a single ROI of standard size to obtain quantitative data on the most severely hypoperfused region. An additional 10 ROIs were placed on the cortex to quantitatively evaluate global cortical perfusion. Mean quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) values were analyzed. RESULTS: The kappa values for qualitative assessment of a perfusion abnormality ranged from 0.55 to 1.0. Coefficients of variation for quantitative assessment of ischemia/infarct region were 27.10% for CBF, 13.33% for CBV, and 4.66% for MTT. Coefficients of variation for quantitative assessment of global cortical perfusion were 11.88% for CBF, 13.66% for CBV, and 3.55% for MTT. The junior CT technologist and neuroradiology fellow showed significant differences compared with other observers for the ischemia/infarct region and global cortical perfusion, respectively. CONCLUSION: Overall, quantitative differences seen in this study would not necessarily affect quality of interpretation of ischemia/infarct region or global cortical perfusion. Therefore, obtaining qualitative and quantitative CTP data can reliably be performed in the clinical setting among observers with various levels of skill and experience when using a uniform and standard technique.

Diffusion anisotropy changes in the brains of professional boxers.

BACKGROUND AND PURPOSE: Professional boxing may result in brain injury. We hypothesize that quantitative MR diffusion imaging may be useful in determining early white matter changes. METHODS: Forty-nine professional boxers (age 30 +/- 4.5 years) and 19 healthy control subjects (age 32 +/- 9.5 years) were imaged on a clinical 1.5T scanner. None of the subjects had neurologic disorder or deficit. The average diffusion constant (D(av)) and diffusion anisotropy (FA) were determined pixel by pixel. Regional diffusion measurements were done in the corpus callosum (CC) and internal capsule (IC). The whole brain diffusion constant (BD(av)) was also determined. Student t test was used to analyze the diffusion difference between boxers and the healthy control subjects. P < .05 was considered statistically significant. RESULTS: Of the 49 professional boxers, 42 had normal conventional MRIs. The remaining 7 boxers had abnormal MR imaging findings dominated by nonspecific white matter disease. There was a significant difference in diffusion and anisotropy measurements in all the boxers compared with the healthy control subjects. In the boxer group, BD(av) increased and FA decreased significantly in the CC and posterior limb of IC. The measured FA and D(av) inversely correlated in regions of CC and IC in boxers but not in healthy control subjects. BD(av) also robustly correlated with both FA and D(av) in the splenium of CC in boxers. CONCLUSION: Increased BD(av) and the decreased FA in the CC and IC may represent preclinical signs of subtle brain injury in professional boxers.

Radiologic estimation of hematoma volume in intracerebral hemorrhage trial by CT scan.

BACKGROUND AND PURPOSE: Therapeutic intervention during the early stages of an intracerebral hemorrhage (ICH) might have value in improving clinical outcomes. During the 73-site International Recombinant Activated Factor VII Intracerebral Hemorrhage Trial, CT techniques were used to monitor the change in hematoma volume in response to treatment. The use of CT imaging technology served 3 functions: to provide accurate measurements of the change in hematoma volume, intraventricular volume (IVH), and edema volume; to evaluate the use of CT scans as a predictor of patient outcomes; and to demonstrate that hematoma volume can serve as a surrogate marker for ICH clinical progression. METHODS: The multicenter clinical trial received institutional review board approval and obtained informed consent from the patient or a legally acceptable representative (waived in a few cases of incapacity, according to local and national regulations). CT scans were used to quantify volumes of hemorrhage and to monitor evolution over a 72-hour period in patients with ICH treated with placebo or 40, 80, or 160 microg/kg of recombinant activated factor VII (rFVIIa). CT image data were transmitted digitally to an imaging laboratory and analyzed by 2 readers masked to patient and treatment data, by using Analyze software, a fully integrated toolkit for interactive display, processing, and measurement of biomedical image data. The use of this software enabled the evaluation of intraclass variability of CT scan interpretations. RESULTS: Interpretations of ICH and IVH volumes of CT scans in patients treated in this study showed minimal intraclass variability. Variability was greatest for interpretations of edema volume. CONCLUSION: These CT assessments of lesions could have value in future early hemostatic interventions in ICH patients.

Detection of intracranial hemorrhage: comparison between gradient-echo images and b(0) images obtained from diffusion-weighted echo-planar sequences.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging (DWI) is commonly used as the initial and sole imaging examination for the detection of acute cerebral infarction, yet it remains controversial whether MR can detect hyperacute (<24 h) hemorrhage. Hemorrhage is best detected with gradient-echo (GRE) T2*-weighted sequences, because of their magnetic susceptibility effects. DWI uses a spin-echo echo-planar technique (EPI) that is more sensitive than spin-echo T2-weighted imaging to susceptibility effects. Our aim was to determine whether the b(0) image from the DWI-EPI sequence is as sensitive as GRE in detecting hemorrhagic lesions on imaging studies performed to identify acute infarction or hemorrhage. METHODS: All MR studies performed for clinically suspected or radiographically confirmed acute infarction or hemorrhage from 2/1/98 to 8/15/99 were retrospectively interpreted by one neuroradiologist in a blinded fashion. The sensitivity of hemorrhage detection, conspicuity of lesions, and diagnostic certainty were compared between the b(0) EPI and GRE sequences. RESULTS: We found 101 acute infarcts, of which 13 were hemorrhagic, as evidenced by the presence of hypointensity within the infarction on the GRE sequence. This finding served as the reference standard for detection of hemorrhage. Hemorrhage was diagnosed with confidence in only seven cases (54%) on b(0) images; 22 acute hematomas were hypointense on GRE images whereas 19 were hypointense on b(0) images (86%); 17 chronic hematomas were depicted on GRE images and 12 on b(0) scans (63%). Punctate hemorrhages and linear cortical staining were detected on 37 GRE studies but on only four b(0) studies. Hemorrhage was always more conspicuous on the GRE sequences. CONCLUSION: b(0) images from a DWI sequence failed to detect minimally hemorrhagic infarctions and small chronic hemorrhages associated with microangiopathy. GRE scans were more sensitive than b(0) images in the detection of these hemorrhages and should be included in emergency brain MR studies for acute infarction, especially when thrombolytic therapy is contemplated.

Hyperintense signal abnormality in subarachnoid spaces and basal cisterns on MR images of children anesthetized with propofol: new fluid-attenuated inversion recovery finding.

BACKGROUND AND PURPOSE: MR imaging is the method of choice for pediatric neuroimaging. Sedation is often needed to suppress patient motion and ensure diagnostic image quality, and propofol is rapidly becoming the preferred anesthetic. The purpose of this study was to document a new finding on fast fluid-attenuated inversion recovery (fast-FLAIR) MR images of children anesthetized with propofol that can be mistaken for subarachnoid space pathologic abnormality. METHODS: A retrospective analysis was conducted of 55 MR images of the brain for children who ranged in age from 1 week to 12 years. Forty-two patients received chloral hydrate, and 13 received propofol anesthetic. Multiplanar MR images were studied to detect the presence or absence of hyperintense signal (artifact) in the subarachnoid spaces and basal cisterns. The T1 values and null times of chloral hydrate, propofol, and CSF were determined in vitro at room temperature by using an inversion recovery pulse sequence at 1.5 T. RESULTS: The fast-FLAIR images of all 13 patients who received propofol had hyperintense signal abnormality. For 10 (77%) of 13 patients, this artifact was in the basal cisterns and subarachnoid spaces overlying the brain convexity. For three (23%) of 13 patients, this artifact was in the convexity region only. Two patients underwent follow-up MR imaging with a nonpropofol anesthetic agent, and the artifact resolved. None of the images of the children who received chloral hydrate had this artifact. The T1 value of chloral hydrate was 0.2 s, of propofol was 1.86 s, and of CSF was 2.32 s at room temperature. CONCLUSION: The fast-FLAIR images of children anesthetized with propofol have artifactual hyperintense signal in the basal cisterns and subarachnoid spaces, and this artifact mimics disease of the subarachnoid space. The T1 value of propofol approaches that of CSF. Depending on the chosen null time, there may be incomplete nulling of signal coming from propofol. To account for this observation, other possible causes include increased CSF pulsation in children creating motion artifact, changes in arterial oxygen concentration intrinsic to propofol or related to the supplemental oxygen normally administered, or changes in CSF protein levels related to propofol binding to proteins for uptake into CSF.

Appearance of meningiomas on diffusion-weighted images: correlating diffusion constants with histopathologic findings.

BACKGROUND AND PURPOSE: Malignant and atypical meningiomas are prone to recurrence and aggressive growth, which affects treatment planning and prognostication. Investigators have used diffusion-weighted imaging and apparent diffusion coefficient (ADC) maps to compare tumor grade and cellularity with the histopathologic findings of intraaxial primary brain neoplasms. The purpose of this study was to determine whether the signal characteristics of meningiomas on diffusion-weighted images correlate with the average diffusion constant (Dav) from ADC maps and histopathologic findings and whether the Dav can reliably distinguish benign from malignant and atypical meningiomas. METHODS: Seventeen patients (13 women and four men; average age, 55 years) with meningiomas were prospectively studied using routine MR imaging and diffusion-weighted imaging with a single-shot gradient-echo echo-planar pulse sequence (6000/100 [TR/TE]) and b values of 0 and 1000. Signal characteristics on routine MR and diffusion-weighted images were compared with the histopathologic findings after resection by using World Health Organization criteria. Dav values were calculated within the tumor mass from ADC maps before resection. RESULTS: Four meningiomas were malignant or atypical (World Health Organization grades II and III). Dav values were lower than normal brain values (average, 0.52 +/- 0.12 x 10(-5) cm2/s; range, 0.45-0.69 x 10(-5) cm2/s) and were hyperintense on diffusion-weighted images and hypointense on ADC maps. Thirteen meningiomas were benign. Dav values were higher than normal brain values (average, 1.03 +/- 0.29 x 10(-5) cm2/s; range, 0.62-1.8 x 10(-5) cm2/s). On diffusion-weighted images and ADC maps, most were isointense. Five benign meningiomas had very high Dav values, bright signal on ADC maps, and distinct histopathologic findings, including microcysts, necrotic infarct, and organizing intratumoral hemorrhage. The difference in Dav values between malignant and benign meningiomas was statistically significant (P < .00029). CONCLUSION: Albeit a small sample size, meningiomas with low Dav tended to be malignant or highly atypical (P < .00029) whereas meningiomas with the highest Dav had increased water content due to either a specific histologic subtype of meningioma or the presence of associated pathologic abnormality.

Diffusion changes in the aging human brain.

BACKGROUND AND PURPOSE: Quantifying changes in the human brain that occur as part of normal aging may help in the diagnosis of diseases that affect the elderly and that cause structural changes in the brain. We sought to assess diffusion changes that are inherently related to brain structure during aging. METHODS: MR scans were obtained from 11 healthy volunteers and 27 patients (ages 26 to 86 years [53.4 +/- 17.0 years]). Images acquired from the patients either showed no abnormalities, contained minimal periventricular white matter changes, or revealed focal lesions. Maps of the average diffusion constant (D(av)) were calculated for each subject. Changes in D(av) were determined with distribution analysis (histogram) for the entire brain and compared with region-of-interest measurements from the periventricular white matter and thalamus. RESULTS: Mean D(av) of the entire brain (0.74 +/- 0.02 x 10(-5) cm2/s) showed weaker age dependency compared with the periventricular white matter D(av)(0.76 +/- 0.04 x 10(-5) cm2/s). The D(av) of the thalamus D(av) (0.75 +/- 0.03 x 10(-5) cm2/s) had no age dependency. The age-dependent changes of entire brain D(av) may be significant for subjects older than 60 years compared with younger subjects. CONCLUSION: In this study, we observed minimal changes in the D(av) of the entire brain with aging. The mean D(av) of the human brain is nearly constant throughout most of adulthood.

Clinical use of diffusion-tensor imaging for diseases causing neuronal and axonal damage.

Diffusion-tensor imaging is an emerging technique that can supply microscopic structural information about tissue in vivo. With this technique it is possible to measure the amount of anisotropy of water diffusion within tissues and to assess the degree to which directionally ordered tissues have lost their normal integrity. This study was performed in four patients to evaluate the feasibility of applying this technique in clinical situations in which there is known or suspected damage to white matter tracts.