Comparison of diameter and perimeter methods for tumor volume calculation.

PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.

Resection of a dominant-hemisphere intraventricular meningioma facilitated by functional magnetic resonance imaging. Case report.

Intraventricular meningiomas of the lateral ventricle occur relatively rarely, but they are often large at the time of detection and present more commonly on the left side. Although the ability to resect these tumors safely has greatly improved over time, standard surgical approaches often traverse cortex close to areas of specific cortical function. Precise cortical mapping of language and sensorimotor cortices can be accomplished noninvasively by using functional magnetic resonance (fMR) imaging. The authors used fMR imaging in planning the cortical incision for resection of a large intraventricular trigone meningioma in the dominant hemisphere of a patient who, postoperatively, suffered no aphasia or hemiparesis. The authors discuss the advantages of mapping cortical function preoperatively with fMR imaging when approaching intraventricular lesions.

Three-dimensional mapping of cortical thickness using Laplace's equation.

We present a novel, computerized method of examining cerebral cortical thickness. The normal cortex varies in thickness from 2 to 4 mm, reflecting the morphology of neuronal sublayers. Cortical pathologies often manifest abnormal variations in thickness, with examples of Alzheimer's disease and cortical dysplasia as thin and thick cortex, respectively. Radiologically, images are 2-D slices through a highly convoluted 3-D object. Depending on the relative orientation of the slices with respect to the object, it is impossible to deduce abnormal cortical thickness without additional information from neighboring slices. We approach the problem by applying Laplace's Equation (V2psi = 0) from mathematical physics. The volume of the cortex is represented as the domain for the solution of the differential equation, with separate boundary conditions at the gray-white junction and the gray-CSF junction. Normalized gradients of psi form a vector field, representing tangent vectors along field lines connecting both boundaries. We define the cortical thickness at any point in the cortex to be the pathlength along such lines. Key advantages of this method are that it is fully three-dimensional, and the thickness is uniquely defined for any point in the cortex. We present graphical results that map cortical thickness everywhere in a normal brain. Results show global variations in cortical thickness consistent with known neuroanatomy. The application of this technique to visualization of cortical thickness in brains with known pathology has broad clinical implications.

Language dominance determined by whole brain functional MRI in patients with brain lesions.

BACKGROUND: Functional MRI (fMRI) is of potential value in determining hemisphere dominance for language in epileptic patients. OBJECTIVE: To develop and validate an fMRI-based method of determining language dominance for patients with a wide range of potentially operable brain lesions in addition to epilepsy. METHODS: Initially, a within-subjects design was used with 19 healthy volunteers (11 strongly right-handed, 8 left-handed) to determine the relative lateralizing usefulness of three different language tasks in fMRI. An automated, hemispheric analysis of laterality was used to analyze whole brain fMRI data sets. To evaluate the clinical usefulness of this method, we compared fMRI-determined laterality with laterality determined by Wada testing or electrocortical stimulation mapping, or both, in 23 consecutive patients undergoing presurgical evaluation of language dominance. RESULTS: Only the verb generation task was reliably lateralizing. fMRI, using the verb generation task and an automated hemispheric analysis method, was concordant with invasive measures in 22 of 23 patients (12 Wada, 11 cortical stimulation). For the single patient who was discordant, in whom a tumor involved one-third of the left hemisphere, fMRI became concordant when the tumor and its reflection in the right hemisphere were excluded from laterality analysis. No significant negative correlation was obtained between lesion size and strength of laterality for the patients with lesions involving the dominant hemisphere. CONCLUSION: This fMRI method shows potential for evaluating language dominance in patients with a variety of brain lesions.

Accuracy of electroencephalographic dipole localization of epileptiform activities associated with focal brain lesions.

We evaluated the accuracy of an electroencephalographic (EEG) localization technique (dipole inverse solution) in a consecutive series of 12 focal intracerebral lesions of diverse etiologies whose EEGs showed interictal spike activity or rhythmic activity at seizure onset. The calculated equivalent dipole was plotted on three axes in the patients' magnetic resonance image, and the distance between the dipole and the lesion margin was measured assuming that the shell of the lesion constituted an epileptogenic region. In all cases the dipole localized closer than 0.8 cm to the nearest lesion margin. In addition, we compared the postsurgical outcome of 6 patients to the dipole localization and the resection margins. In all 6 patients in whom the dipole, and hence the estimated seizure generator, was removed the surgical outcome was favorable. We conclude that the inverse solution algorithm is a promising method for using the scalp EEG to localize the sources of electrical activity in the human brain in routine clinical electroencephalography and provides three-dimensional data not available from conventional analysis.

Cortical activation MR studies in brain disorders.

Principles and clinical applications of functional MR imaging activation studies are presented. The physical and physiologic basis for cerebral blood volume-, cerebral blood flow-, and oxygenation-based functional MR imaging techniques are reviewed. The methodology of blood oxygen level dependent (BOLD) functional MR imaging is emphasized. Applications to presurgical mapping of sensorimotor and language function in patients with vascular malformations, tumors, and other lesions near critical cortical areas are illustrated. Important new applications to neuropsychiatric diseases are highlighted.

Stereotactic transcranial magnetic stimulation: correlation with direct electrical cortical stimulation.

OBJECTIVE: To evaluate stereotactic transcranial magnetic stimulation (TMS) as a tool for presurgical functional mapping of human motor cortex. METHODS: Transcranial magnetic stimulation using a frameless stereotactic system was performed in two patients with tumors near the central sulcus. TMS motor function maps were plotted on the patients' three-dimensional volumetric magnetic resonance imaging data and compared with direct electrical cortical stimulation at surgery with the patient under local anesthesia. RESULTS: Stereotactic TMS was well tolerated by both patients and was consistent with known somatotopic representation of human motor cortex. The results demonstrated a good correlation between the TMS and electrical cortical stimulation maps, with all TMS responses eliciting more than 75% of the maximum motor evoked potential falling within 1 cm of the electrical cortical stimulation site. CONCLUSIONS: Our findings indicate that stereotactic TMS is feasible and can provide accurate noninvasive localization of cortical motor function. It may prove to be a useful method for presurgical planning.

Location of language in the cortex: a comparison between functional MR imaging and electrocortical stimulation.

PURPOSE: To determine the accuracy of functional MR imaging in locating language areas for planning surgical resection. METHODS: Intraoperative photographs were digitized and overlaid on functional MR language maps. The sensitivity and specificity of functional MR imaging for identifying language areas were determined for five different language tasks by comparing functional MR areas of language activation with results of electrocortical stimulation. A match was considered to occur if an activated area contacted overlapped, or surrounded a language tag. The borders of the activation areas were extended by 1 and 2 cm to determine whether the number of matches changed. Language and nonlanguage tag matches were tabulated separately. RESULTS: Sensitivity/specificity for all patients and all language tasks ranged from 81%/53% for areas that touched to 92%/0% for areas separated by 2 cm. Individual language tasks were not as sensitive as a battery of language tasks combined. Location of language areas varied among subjects for a given task and among tasks for a given subject. CONCLUSION: Functional MR imaging should be considered a useful presurgical planning tool for mapping cortical language areas, because it is sensitive, it provides increased time for planning before surgery, and it is noninvasive.

Contrast-to-noise ratio in functional MRI of relative cerebral blood volume with sprodiamide injection.

The purpose of this study was to investigate the dependence of contrast-to-noise ratio (CNR) on the dose and rate of sprodiamide injection in magnetic resonance relative cerebral blood volume (rCBV) imaging. rCBV maps for 35 normal volunteers were constructed from dynamic MR image sets acquired with echo-planar spin-echo imaging after intravenous injection of sprodiamide. Doses of .1, .2, and .3 mmol/kg, at rates of 2 ml/second and 5 ml/second, were tested. CNRs and blood/volume ratios of gray to white matter were computed. CNR depended on dose (P < .0001) but was independent of injection rate (P < .69). rCBV ratios of gray to white matter were dose independent (P < .38) and rate independent (P < .97). The dependence of CNR on dose, but not injection rate, has practical implications in optimal protocol design. The independence of gray/white ratios supports the theory underlying the generation of rCBV maps.

Functional magnetic resonance imaging and transcranial magnetic stimulation: complementary approaches in the evaluation of cortical motor function.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) represent different approaches to mapping the motor cortex. fMRI identifies areas of hemodynamic changes during task performance while TMS provides electrophysiologic data concerning the localization and density of cortical motoneurons. Here we define the spatial correlation between fMRI and TMS maps and compared them with direct electrical cortical stimulation (ECS). We performed fMRI at 1.5 T on 3 normal subjects and 2 patients with mass lesions near the central sulcus using a multislice, asymmetric, spin-echo, echo-planar pulse sequence during the performance of a motor task. We also performed focal TMS with surface EMG recordings from the muscles primarily involved in the fMRI task. We coregistered the stimulation sites in real time with the fMRI maps using a frameless stereotactic system. In both patients we also performed ECS of the cortex during surgery under local anesthesia. fMRI maps were validated by the electrophysiologic data both pre- and intraoperatively. Our results suggest that regions of fMRI activation correspond spatially to areas of highest motoneuron density as demonstrated by electrophysiologic techniques.

Functional MRI localization of language in a 9-year-old child.

BACKGROUND: Localizing critical brain functions such as language in children is difficult and generally requires invasive techniques. Recently sensory, motor and language functions in adults have been mapped to specific brain locations using functional imaging techniques. Of these techniques, functional MRI (fMRI) is the least invasive and has the highest spatial and temporal resolution. Its use in adults is well documented but application to children has not been as well described. In the present study lateralization and localization of language was evaluated with fMRI prior to epilepsy surgery in a nine-year-old male with complex partial seizures, attentional difficulty and decreased verbal proficiency. METHODS: Two language paradigms well studied in adults (read, verb generation) and two additional language paradigms (antonym generation, latter fluency) were studied using whole brain fMRI after stimulus items and timing were adjusted to achieve the desired performance level during imaging. The patient was also conditioned to the magnet environment prior to imaging. RESULTS: Word reading and letter fluency tasks produced lateralized and localized activation similar to that seen in adults. The patient had no language deficits following an anterior 2/3 dominant temporal lobe resection. CONCLUSIONS: With modifications of protocols such as those detailed in this report, this non-invasive method for localizing language function is feasible for the presurgical evaluation of children as well being applicable for a variety of developmental language issues.

Functional magnetic resonance imaging for intracranial navigation.

Functional MR imaging can provide accurate anatomic and physiologic localization of human cortical function. This new method of noninvasive cortical mapping appears to be valuable preoperatively for risk assessment, therapeutic decision making and surgical planning. The integrated volume rendering of brain surface topography, cortical veins, structural lesion, and sites of functional activation is also useful intraoperatively for defining cortical resection boundaries in patients with lesions in critical areas.

Echo-planar MR cerebral blood volume mapping of gliomas. Clinical utility.

Neovascularization is a common phenomenon in gliomas. MR imaging cerebral blood volume (CBV) mapping utilizes ultrasfast echo-planar imaging and simultaneous use of gadolinium-based contrast material. To determine the utility of MR CBV mapping in the clinical evaluation of gliomas, we followed 15 patients with serial studies. This technique provided functional information that was not evident with conventional CT or MR imaging. Low-grade tumors demonstrated homogeneously low CBV, while high-grade tumors often showed areas of both high and low CBV. The maximum tumor CBV/white matter ratio was compared between low- (n = 3) and high-grade gliomas (n = 5) in patients without previous treatment and with histologic verification (n = 8) and was significantly higher in high-grade gliomas (p < 0.01). High CBV foci in nonenhancing tumor areas were present in 2 cases. The distinction between radiation necrosis and active tumor could be made correctly in 3 of 4 cases. The information provided by MR CBV mapping has the potential to be an adjunct in the clinical care of glioma patients.

Functional magnetic resonance imaging for cortical mapping in pediatric neurosurgery.

Currently there is considerable interest in applying functional imaging modalities to the problem of cortical localization. We present the case of a 15-year-old boy with a seizure disorder related to a tumor in the dominant supplementary motor area. This case illustrates the usefulness of functional magnetic resonance imaging as a new imaging tool for localization of cortical function in younger patients. The functional magnetic resonance imaging provided an anatomically accurate topographic map of operative site and subcortical structures along with relevant functional cortex. This information was useful for both presurgical planning and intraoperative localization. Validation of the technique in this instance was confirmed with intraoperative cortical motor mapping and the postoperative result.

Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings.

PURPOSE: To assess the utility of magnetic resonance (MR) cerebral blood volume (CBV) maps in the evaluation of gliomas. MATERIALS AND METHODS: CBV maps from 19 patients with histologically proved gliomas were calculated from dynamic MR image sets acquired with echo-planar spin-echo imaging after intravenous injection of gadolinium-based contrast material. RESULTS: The maximum CBV varied from 0.82 to 5.40 in the high-grade group (n = 13) and from 1.01 to 1.21 in the low-grade group (n = 6). The difference was statistically significant. Maximum CBV was associated with mitotic activity and vascularity, but not with cellular atypia, endothelial proliferation, necrosis, or cellularity. CONCLUSION: MR CBV maps provided diagnostic information not available with conventional MR imaging in six cases and offers a functional parameter for assessing glioma grade and regions of focal activity.

Susceptibility contrast imaging of cerebral blood volume: human experience.

Magnetic resonance (MR) can offer a unique window on the structure/function relationships in the brain, by utilizing the established link between tissue function, metabolism, and hemodynamics. This report focuses on recent applications of MR-based cerebral blood volume (CBV) imaging in humans. Our methodology uses high-speed "single-shot" or echo planar imaging techniques, which provide the necessary temporal resolution for mapping the rapid cerebral transit of contrast agents. These MR CBV mapping techniques have been used to study normal human brain task activation and in the clinical study of patients with brain tumors. In the latter, positron emission tomography imaging was used for functional metabolic and CBV correlation. Susceptibility contrast CBV imaging should allow us to improve our understanding of the relationship between the detailed physiology and morphology of the microvascular bed and functional attributes of the brain. These techniques can be applied to understanding fundamental questions of cognitive neuroscience and can aid in improving diagnostic sensitivity and specificity in various neuropathologies.

Functional mapping of the human visual cortex by magnetic resonance imaging.

Knowledge of regional cerebral hemodynamics has widespread application for both physiological research and clinical assessment because of the well-established interrelation between physiological function, energy metabolism, and localized blood supply. A magnetic resonance technique was developed for quantitative imaging of cerebral hemodynamics, allowing for measurement of regional cerebral blood volume during resting and activated cognitive states. This technique was used to generate the first functional magnetic resonance maps of human task activation, by using a visual stimulus paradigm. During photic stimulation, localized increases in blood volume (32 +/- 10 percent, n = 7 subjects) were detected in the primary visual cortex. Center-of-mass coordinates and linear extents of brain activation within the plane of the calcarine fissure are reported.

Epiphyseal marrow in infancy: MR imaging.

Hypointense epiphyseal marrow on T1-weighted magnetic resonance images often suggests disease. To determine whether hypointense marrow sometimes represents normal red marrow in a recently ossified epiphyseal center, the authors studied 38 infants without known marrow disease. Patients with hypointense epiphyseal marrow on T1-weighted images were younger (3.9 months +/- 3.2) than those with hyperintense marrow (9.6 months +/- 3.9) (P less than .001). T1-weighted imaging and histologic correlation were also performed in animals. The signal was hypointense and the marrow was red in the epiphyseal centers of all newborn animals, while all 6-week-old animals had hyperintense signal and yellow marrow. The authors conclude that hypointense marrow on T1-weighted images represents normal red marrow in a recently formed ossification center in newborn rabbits and lambs, and the same is probably true in humans. Epiphyseal marrow becomes hyperintense within a few months of development of the secondary center of ossification.

Contrast agents and cerebral hemodynamics.

Contrast-enhanced magnetic resonance imaging of regional cerebral hemodynamics is discussed. Techniques for measuring cerebral blood volume (CBV) have been validated in animal models and have recently been applied to human studies. Factors affecting CBV measurement in pathologic tissue are addressed. Extension of these techniques to the measurement of cerebral blood flow is presented.

Functional studies of the human brain using high-speed magnetic resonance imaging.

Dramatic technical advances in magnetic resonance imaging (MRI or NMR) scanning speed and recent governmental approval for the routine use of NMR contrast agents have yielded techniques for quantitative imaging of cerebral hemodynamics. The technical basis of ultrafast imaging, the methodology of dynamic imaging with contrast agents, and results in normal subjects and patients are presented.