Identification of the Language Network from Resting-State fMRI in Patients with Brain Tumors: How Accurate Are Experts?

BACKGROUND AND PURPOSE: Resting-state fMRI helps identify neural networks in presurgical patients who may be limited in their ability to undergo task-fMRI. The purpose of this study was to determine the accuracy of identifying the language network from resting-state-fMRI independent component analysis (ICA) maps. MATERIALS AND METHODS: Through retrospective analysis, patients who underwent both resting-state-fMRI and task-fMRI were compared by identifying the language network from the resting-state-fMRI data by 3 reviewers. Blinded to task-fMRI maps, these investigators independently reviewed resting-state-fMRI ICA maps to potentially identify the language network. Reviewers ranked up to 3 top choices for the candidate resting-state-fMRI language map. We evaluated associations between the probability of correct identification of the language network and some potential factors. RESULTS: Patients included 29 men and 14 women with a mean age of 41 years. Reviewer 1 (with 17 years' experience) demonstrated the highest overall accuracy with 72%; reviewers 2 and 3 (with 2 and 7 years' experience, respectively) had a similar percentage of correct responses (50% and 55%). The highest accuracy used ICA50 and the top 3 choices (81%, 65%, and 60% for reviewers 1, 2, and 3, respectively). The lowest accuracy used ICA50, limiting each reviewer to the top choice (58%, 35%, and 42%). CONCLUSIONS: We demonstrate variability in the accuracy of blinded identification of resting-state-fMRI language networks across reviewers with different years of experience.

Discrimination between Glioblastoma and Solitary Brain Metastasis: Comparison of Inflow-Based Vascular-Space-Occupancy and Dynamic Susceptibility Contrast MR Imaging.

BACKGROUND AND PURPOSE: Accurate differentiation between glioblastoma and solitary brain metastasis is of vital importance clinically. This study aimed to investigate the potential value of the inflow-based vascular-space-occupancy MR imaging technique, which has no need for an exogenous contrast agent, in differentiating glioblastoma and solitary brain metastasis and to compare it with DSC MR imaging. MATERIALS AND METHODS: Twenty patients with glioblastoma and 22 patients with solitary brain metastasis underwent inflow-based vascular-space-occupancy and DSC MR imaging with a 3T clinical scanner. Two neuroradiologists independently measured the maximum inflow-based vascular-space-occupancy-derived arteriolar CBV and DSC-derived CBV values in intratumoral regions and peritumoral T2-hyperintense regions, which were normalized to the contralateral white matter (relative arteriolar CBV and relative CBV, inflow-based vascular-space-occupancy relative arteriolar CBV, and DSC-relative CBV). The intraclass correlation coefficient, Student t test, or Mann-Whitney U test and receiver operating characteristic analysis were performed. RESULTS: All parameters of both regions had good or excellent interobserver reliability (0.74∼0.89). In peritumoral T2-hyperintese regions, DSC-relative CBV (P < .001), inflow-based vascular-space-occupancy arteriolar CBV (P = .001), and relative arteriolar CBV (P = .005) were significantly higher in glioblastoma than in solitary brain metastasis, with areas under the curve of 0.94, 0.83, and 0.72 for discrimination, respectively. In the intratumoral region, both inflow-based vascular-space-occupancy arteriolar CBV and relative arteriolar CBV were significantly higher in glioblastoma than in solitary brain metastasis (both P < .001), with areas under the curve of 0.91 and 0.90, respectively. Intratumoral DSC-relative CBV showed no significant difference (P = .616) between the 2 groups. CONCLUSIONS: Inflow-based vascular-space-occupancy has the potential to discriminate glioblastoma from solitary brain metastasis, especially in the intratumoral region.

Preoperative Mapping of the Supplementary Motor Area in Patients with Brain Tumor Using Resting-State fMRI with Seed-Based Analysis.

BACKGROUND AND PURPOSE: The supplementary motor area can be a critical region in the preoperative planning of patients undergoing brain tumor resection because it plays a role in both language and motor function. While primary motor regions have been successfully identified using resting-state fMRI, there is variability in the literature regarding the identification of the supplementary motor area for preoperative planning. The purpose of our study was to compare resting-state fMRI to task-based fMRI for localization of the supplementary motor area in a large cohort of patients with brain tumors presenting for preoperative brain mapping. MATERIALS AND METHODS: Sixty-six patients with brain tumors were evaluated with resting-state fMRI using seed-based analysis of hand and orofacial motor regions. Rates of supplementary motor area localization were compared with those in healthy controls and with localization results by task-based fMRI. RESULTS: Localization of the supplementary motor area using hand motor seed regions was more effective than seeding using orofacial motor regions for both patients with brain tumor (95.5% versus 34.8%, P < .001) and controls (95.2% versus 45.2%, P < .001). Bilateral hand motor seeding was superior to unilateral hand motor seeding in patients with brain tumor for either side (95.5% versus 75.8%/75.8% for right/left, P < .001). No difference was found in the ability to identify the supplementary motor area between patients with brain tumors and controls. CONCLUSIONS: In addition to task-based fMRI, seed-based analysis of resting-state fMRI represents an equally effective method for supplementary motor area localization in patients with brain tumors, with the best results obtained with bilateral hand motor region seeding.

American Society of Functional Neuroradiology-Recommended fMRI Paradigm Algorithms for Presurgical Language Assessment.

INTRODUCTION: Functional MR imaging is increasingly being used for presurgical language assessment in the treatment of patients with brain tumors, epilepsy, vascular malformations, and other conditions. The inherent complexity of fMRI, which includes numerous processing steps and selective analyses, is compounded by institution-unique approaches to patient training, paradigm choice, and an eclectic array of postprocessing options from various vendors. Consequently, institutions perform fMRI in such markedly different manners that data sharing, comparison, and generalization of results are difficult. The American Society of Functional Neuroradiology proposes widespread adoption of common fMRI language paradigms as the first step in countering this lost opportunity to advance our knowledge and improve patient care. LANGUAGE PARADIGM REVIEW PROCESS: A taskforce of American Society of Functional Neuroradiology members from multiple institutions used a broad literature review, member polls, and expert opinion to converge on 2 sets of standard language paradigms that strike a balance between ease of application and clinical usefulness. ASFNR RECOMMENDATIONS: The taskforce generated an adult language paradigm algorithm for presurgical language assessment including the following tasks: Sentence Completion, Silent Word Generation, Rhyming, Object Naming, and/or Passive Story Listening. The pediatric algorithm includes the following tasks: Sentence Completion, Rhyming, Antonym Generation, or Passive Story Listening. DISCUSSION: Convergence of fMRI language paradigms across institutions offers the first step in providing a "Rosetta Stone" that provides a common reference point with which to compare and contrast the usefulness and reliability of fMRI data. From this common language task battery, future refinements and improvements are anticipated, particularly as objective measures of reliability become available. Some commonality of practice is a necessary first step to develop a foundation on which to improve the clinical utility of this field.

Presurgical Brain Mapping of the Ventral Somatomotor Network in Patients with Brain Tumors Using Resting-State fMRI.

BACKGROUND AND PURPOSE: Resting-state fMRI readily identifies the dorsal but less consistently the ventral somatomotor network. Our aim was to assess the relative utility of resting-state fMRI in the identification of the ventral somatomotor network via comparison with task-based fMRI in patients with brain tumor. MATERIALS AND METHODS: We identified 26 surgically naïve patients referred for presurgical fMRI brain mapping who had undergone both satisfactory ventral motor activation tasks and resting-state fMRI. Following standard preprocessing for task-based fMRI and resting-state fMRI, general linear model analysis of the ventral motor tasks and independent component analysis of resting-state fMRI were performed with the number of components set to 20, 30, 40, and 50. Visual overlap of task-based fMRI and resting-state fMRI at different component levels was assessed and categorized as full match, partial match, or no match. Rest-versus-task-fMRI concordance was calculated with Dice coefficients across varying fMRI thresholds before and after noise removal. Multithresholded Dice coefficient volume under the surface was calculated. RESULTS: The ventral somatomotor network was identified in 81% of patients. At the subject level, better matches between resting-state fMRI and task-based fMRI were seen with an increasing order of components (53% of cases for 20 components versus 73% for 50 components). Noise-removed group-mean volume under the surface improved as component numbers increased from 20 to 50, though ANOVA demonstrated no statistically significant difference among the 4 groups. CONCLUSIONS: In most patients, the ventral somatomotor network can be identified with an increase in the probability of a better match at a higher component number. There is variable concordance of the ventral somatomotor network at the single-subject level between resting-state and task-based fMRI.

Cerebrovascular reactivity mapping: an evolving standard for clinical functional imaging.

SUMMARY: This review article explains the methodology of breath-hold cerebrovascular reactivity mapping, both in terms of acquisition and analysis, and reviews applications of this method to presurgical mapping, particularly with respect to blood oxygen level-dependent fMRI. Its main application in clinical fMRI is for the assessment of neurovascular uncoupling potential. Neurovascular uncoupling is potentially a major limitation of clinical fMRI, particularly in the setting of mass lesions in the brain such as brain tumors and intracranial vascular malformations that are associated with alterations in regional hemodynamics on either an acquired or congenital basis. As such, breath-hold cerebrovascular reactivity mapping constitutes an essential component of quality control analysis in clinical fMRI, particularly when performed for presurgical mapping of eloquent cortex. Exogenous carbon dioxide challenges used for cerebrovascular reactivity mapping will also be discussed, and their applications to the evaluation of cerebrovascular reserve and cerebrovascular disease will be described.

Role of semantic paradigms for optimization of language mapping in clinical FMRI studies.

BACKGROUND AND PURPOSE: The optimal paradigm choice for language mapping in clinical fMRI studies is challenging due to the variability in activation among different paradigms, the contribution to activation of cognitive processes other than language, and the difficulties in monitoring patient performance. In this study, we compared language localization and lateralization between 2 commonly used clinical language paradigms and 3 newly designed dual-choice semantic paradigms to define a streamlined and adequate language-mapping protocol. MATERIALS AND METHODS: Twelve healthy volunteers performed 5 language paradigms: Silent Word Generation, Sentence Completion, Visual Antonym Pair, Auditory Antonym Pair, and Noun-Verb Association. Group analysis was performed to assess statistically significant differences in fMRI percentage signal change and lateralization index among these paradigms in 5 ROIs: inferior frontal gyrus, superior frontal gyrus, middle frontal gyrus for expressive language activation, middle temporal gyrus, and superior temporal gyrus for receptive language activation. RESULTS: In the expressive ROIs, Silent Word Generation was the most robust and best lateralizing paradigm (greater percentage signal change and lateralization index than semantic paradigms at P < .01 and P < .05 levels, respectively). In the receptive region of interest, Sentence Completion and Noun-Verb Association were the most robust activators (greater percentage signal change than other paradigms, P < .01). All except Auditory Antonym Pair were good lateralizing tasks (the lateralization index was significantly lower than other paradigms, P < .05). CONCLUSIONS: The combination of Silent Word Generation and ≥1 visual semantic paradigm, such as Sentence Completion and Noun-Verb Association, is adequate to determine language localization and lateralization; Noun-Verb Association has the additional advantage of objective monitoring of patient performance.

Polymer nanoparticles--a novel strategy for administration of Paclitaxel in cancer chemotherapy.

The main challenge encountered while treating using Paclitaxel (PTX) is its poor solubility in aqueous solutions. The cremophor used in the formulation can cause various side effects such as hypersensitivity, myelosuppression and neurotoxicity and also leads to non-specific distribution in tumor and normal tissues. Since the structure of Paclitaxel does not possess a functional group, it is not easy to manipulate to enhance the solubility. Such limitations can be overcome by delivering Paclitaxel with the aid of drug delivery systems such as polymeric micelles, nanoparticles, hydrogels and liposomes. The review discusses various approaches of Paclitaxel delivery via polymeric nanoparticles. It focuses on the passive and active targeting of Paclitaxel.

CT-guided injection of the anterior and middle scalene muscles: technique and complications.

BACKGROUND AND PURPOSE: Anterior scalene block is a helpful diagnostic test for NTOS and a good predictor of surgical outcome. The purpose of this study was to describe the technique, success rate, and complications associated with CT-guided anesthetic and botulinum toxin injection of the ASM/MSM in patients with NTOS symptoms. MATERIALS AND METHODS: One hundred six participants (mean age, 41.5 ± 10 years; 80 women) were identified via a retrospective review of medical records for CT-guided scalene blocks. The procedure was evaluated regarding the technical success, defined as satisfactory detection of the ASM/MSM; intramuscular needle placement; intramuscular injection of contrast; appropriate delivery of medication; and frequency of unintended BP block or other complications. We also determined the outcome of patients who underwent surgery following the block. RESULTS: Study participants underwent 146 scalene injections, 83 blocks, and 63 chemodenervations, which were included in this investigation. In all cases, detection of the ASM/MSM and intramuscular needle placement was satisfactory. Postprocedural complications included 5 (3.4%) temporary BP blocks, 1 patient with (0.7%) Horner sign, 7 (4.8%) needle-induced pain reports, 1 (0.7%) case of dysphagia, and 2 (1.4%) instances of muscle weakness. There were no major complications reported. The rate of good outcome following surgery was the same in patients with positive versus negative blocks, 30/43 (70%) versus 5/7 (71%), respectively. CONCLUSIONS: CT guidance is a useful adjunct in performing accurate ASM/MSM blocks with a low rate of minor complications.

The evolution of clinical functional imaging during the past 2 decades and its current impact on neurosurgical planning.

BOLD fMRI has, during the past decade, made a major transition from a purely research imaging technique to a viable clinical technique used primarily for presurgical planning in patients with brain tumors and other resectable brain lesions. This review article briefly examines the history and evolution of clinical functional imaging, with particular emphasis on how the use of BOLD fMRI for neurosurgical planning has changed during the past 2 decades. Even more important, this article describes the many published studies during that same period that have examined the overall clinical impact that BOLD and DTI have made on surgical planning.

Insights into adult postlesional language cortical plasticity provided by cerebral blood oxygen level-dependent functional MR imaging.

BOLD fMRI has provided new insights into postlesional brain language plasticity by providing a noninvasive in vivo approach to evaluate longitudinal changes in brain cortical activation during performance of language tasks. Specifically, BOLD fMRI has provided the opportunity to investigate not only changes in eloquent language cortex resulting from different types of brain pathology such as brain tumors, stroke, and epilepsy but also changes in eloquent language cortex occurring as a result of actual surgical resection of diseased but, nevertheless, partially functional tissue. In addition to reviewing the literature relating to stroke and epilepsy-related language plasticity as well as the more intriguing phenomenon of postsurgical plasticity in the setting of brain tumors, 2 unusual cases illustrating this latter manifestation of language plasticity are briefly described in this review article.

Pathophysiology of altered consciousness during seizures: Subtraction SPECT study.

BACKGROUND: The mechanisms underlying altered consciousness during seizures are poorly understood. Previous clinicopathologic studies suggest a role for the thalamus and upper brainstem in consciousness mechanisms. OBJECTIVE: To examine blood flow changes associated with altered consciousness during seizures. METHODS: Seventy-one patients with epilepsy who underwent video-EEG monitoring and ictal/interictal SPECT were studied. Patients were divided into three groups depending on their conscious state during seizures: 1) complete impairment of consciousness (CI), 2) no impairment of consciousness (NI), or 3) uncertain impairment of consciousness (UI). The distribution of blood flow changes during these seizures was assessed by subtraction (ictal - interictal) SPECT co-registered to MRI. Conscious state was assessed in relation to secondary ictal hyperperfusion in subcortical regions (i.e., thalamus and upper brainstem). RESULTS: Impairment of consciousness showed a strong association with secondary hyperperfusion in the thalamic/upper brainstem region (p = 0.01), occurring in 92% (45/49) of CI, 69% (9/13) of UI, and 11% (1/9) of NI. CONCLUSIONS: These findings are consistent with a role for the thalamus and upper brainstem in consciousness mechanisms. The authors suggest that the spread of epileptic discharges or a trans-synaptic activation (diaschisis) of these structures is an important mechanism in the alteration of consciousness during seizures. Variance in the results may be due to differences in timing of radioisotope injection, sensitivity of the subtraction SPECT technique, and the ability to clinically assess the conscious state.

Topography of somatosensory processing: cerebral lateralization and focused attention.

Healthy dextrals underwent fMRI during a task of graphesthesia requiring detection of any number written consecutively from an otherwise random number sequence. Test conditions included (1) focus on unilateral right hand stimuli, (2) focus on unilateral left hand stimuli, (3) focus on right hand only during bilateral hand stimulation, (4) focus on left hand only during bilateral hand stimulation, and (5) rest. Attention to unilateral hand stimulation produced bihemispheric activation with minimal or no activation of ipsilateral primary sensorimotor region. Attention to unilateral left hand stimuli resulted in more activation than attention to unilateral right hand stimuli. Stimulation of the nonattended hand activated the contralateral somatosensory area, but to a lesser spatial extent than attended stimuli. Comparing focused attention to the left versus right side during identical sensory inputs (i.e., bilateral hand stimulation), focused attention to the right hand increased activation in the left somatosensory region, but focused attention to the left hand increased activation in both cerebral hemispheres. Thus, focused attention to unilateral somatosensory stimuli produces bilateral cerebral activation, but the increase in blood flow is greater in the contralateral hemisphere. Unattended stimuli activate the contralateral primary somatosensory area. Left/right asymmetries were demonstrated consistent with cerebral lateralization.

Now you see it, now you don't: statistical and methodological considerations in fMRI.

We illustrate the effects of statistical threshold, spatial clustering, voxel size, and two approaches to multiple comparison correction on fMRI results. We first analyzed fMRI images obtained from a single subject during a noun-verb matching task. Data were analyzed with Statistical Parametric Mapping (SPM) using two different voxel sizes, and results were displayed at three different levels of statistical significance. At each statistical threshold, results were first uncorrected for multiple comparisons and spatial extent and then presented using a spatial extent cluster of 20 voxels. We then statistically controlled the Type I error rate associated with multiple comparisons by using the false discovery rate and by the random field adjustment for false-positive rate used by SPM. We also examined group results from language and graphesthesia paradigms at three levels of statistical significance. In all circumstances, apparent random activations decreased as more conservative statistical approaches were employed, but activation in areas considered to be functionally significant was also reduced. These issues are important in the choice of analytic approach and interpretation of fMRI results, with clear implications for the surgical management of individual patients when fMRI results are used to delineate specific areas of eloquent cortex.

Orbital cellulitis due to occult orbital lymphangioma.

A 12-year-old female patient with atypical orbital and periorbital cellulitis was found to have an occult lymphangioma of the orbit. Recognition of this entity provided an explanation for the atypical features of the case and guided appropriate medical management.

Initial angiographic appearance of intracranial vascular occlusions in acute stroke as a predictor of outcome of thrombolysis: initial experience.

PURPOSE: To determine whether the initial angiographic morphology and location of intracranial arterial occlusions in acute stroke are reliable predictors of success of thrombolysis. MATERIALS AND METHODS: Thirty-three intracranial occlusions were studied in 32 patients who underwent intraarterial thrombolysis with urokinase within 6 hours from clinical onset of stroke symptoms. The initial angiographic appearance of each occlusion was categorized as cutoff, tapered, meniscus, tram-track, or tandem. Following thrombolysis, outcomes were classified as complete, partial, or no recanalization. RESULTS: Complete recanalization was accomplished in 17 of the 33 lesions, partial recanalization in nine, and no effect in seven. Tram-track (n = 3) and tapered (n = 7) lesions demonstrated the highest rates of at least partial recanalization (100% and 86%, respectively), whereas cutoff lesions (n = 13) demonstrated the lowest rate (69%). Intracranial hemorrhage was associated with higher doses of urokinase. Complete recanalization success rates were 60% for M1 lesions (n = 10), 43% for M2 or A2 lesions (n = 14), and 33% for M3 lesions (n = 3). Vertebrobasilar lesion (n = 5) success rates for complete and at least partial recanalization were 80% and 100%, respectively. CONCLUSION: Relationships were found to exist between the success rate of recanalization and initial angiographic lesion location and morphology, which represent important trends; however, further studies with a larger sample size are needed.