Adding dynamics to the Human Connectome Project with MEG.

The Human Connectome Project (HCP) seeks to map the structural and functional connections between network elements in the human brain. Magnetoencephalography (MEG) provides a temporally rich source of information on brain network dynamics and represents one source of functional connectivity data to be provided by the HCP. High quality MEG data will be collected from 50 twin pairs both in the resting state and during performance of motor, working memory and language tasks. These data will be available to the general community. Additionally, using the cortical parcellation scheme common to all imaging modalities, the HCP will provide processing pipelines for calculating connection matrices as a function of time and frequency. Together with structural and functional data generated using magnetic resonance imaging methods, these data represent a unique opportunity to investigate brain network connectivity in a large cohort of normal adult human subjects. The analysis pipeline software and the dynamic connectivity matrices that it generates will all be made freely available to the research community.

The Human Connectome Project: a data acquisition perspective.

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Predictive value of hippocampal MR imaging-based high-dimensional mapping in mesial temporal epilepsy: preliminary findings.

BACKGROUND AND PURPOSE: We objectively assessed surface structural changes of the hippocampus in mesial temporal sclerosis (MTS) and assessed the ability of large-deformation high-dimensional mapping (HDM-LD) to demonstrate hippocampal surface symmetry and predict group classification of MTS in right and left MTS groups compared with control subjects. METHODS: Using eigenvector field analysis of HDM-LD segmentations of the hippocampus, we compared the symmetry of changes in the right and left MTS groups with a group of 15 matched controls. To assess the ability of HDM-LD to predict group classification, eigenvectors were selected by a logistic regression procedure when comparing the MTS group with control subjects. RESULTS: Multivariate analysis of variance on the coefficients from the first 9 eigenvectors accounted for 75% of the total variance between groups. The first 3 eigenvectors showed the largest differences between the control group and each of the MTS groups, but with eigenvector 2 showing the greatest difference in the MTS groups. Reconstruction of the hippocampal deformation vector fields due solely to eigenvector 2 shows symmetrical patterns in the right and left MTS groups. A "leave-one-out" (jackknife) procedure correctly predicted group classification in 14 of 15 (93.3%) left MTS subjects and all 15 right MTS subjects. CONCLUSION: Analysis of principal dimensions of hippocampal shape change suggests that MTS, after accounting for normal right-left asymmetries, affects the right and left hippocampal surface structure very symmetrically. Preliminary analysis using HDM-LD shows it can predict group classification of MTS and control hippocampi in this well-defined population of patients with MTS and mesial temporal lobe epilepsy (MTLE).

Effect of recombinant human bone morphogenetic protein-2 on fracture healing in a goat tibial fracture model.

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP-2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP-2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP-2/ACS treated tibiae. At 6 weeks, the rhBMP-2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP-2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP-2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP-2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP-2/ACS treatment. The increased callus volume associated with rhBMP-2 treatment produced only moderate increases in strength and stiffness.

Coralline hydroxyapatite bone-graft substitutes in a canine metaphyseal defect model. Radiographic-histometric correlation.

Radiographic and histometric evaluation of a new form of bone-graft substitute derived from reef-building sea coral was performed in a canine metaphyseal defect model. Blocks of this material were implanted into the proximal tibial metaphyses of eight dogs, with radiographic densitometry and harvesting performed at two, four, six, and 12 months. Histometric analysis demonstrated progressive apposition of host compact bone at the margins and trabecular bone at the interior of the implants with time following surgery. Corrected transmission density determinations correlated significantly with degree of osseous ingrowth (R = -0.78), void volume fraction (R = 0.88), and postoperative interval (R = 0.88). These results support the successful early application of coralline hydroxyapatite bone-graft substitutes as an alternative to autogenous grafting in the clinical setting, and indicate that the course of incorporation into host bone can be noninvasively monitored using densitometric techniques.

Coralline hydroxyapatite bone-graft substitutes in a canine diaphyseal defect model. Radiographic-histometric correlation.

Radiographic and histometric evaluation of a new form of bonegraft substitute derived from reef-building sea coral was performed in a canine diaphyseal defect model. Comparably sized blocks of this material and iliac crest autograft were placed into bilateral surgically created cortical windows in the distal radial diaphyses of 14 dogs. Representative graft specimens of both types underwent densitometric radiography and harvesting at 3, 6, 12, 24, and 48 months. Histometric analysis of implant specimens revealed satisfactory union and native osseous ingrowth at all time intervals. Graft specimens exhibited adequate union with scant host bone ingrowth at three months, but subsequent progressive appositional closure of cancellous spaces during the ensuing 45 months. Volume fraction and mean width of host bone remained stable in the implants but increased in the grafts due to neocortex formation. Stereologic distribution of bone was homogeneous in both implant and graft specimens, and no evidence for biodegradation of the former was observed. Corrected transmission density determinations accurately reflected these differences but correlated significantly with volume fractions and tissue widths of bone and soft tissue only in the autografts. These results support the successful early application of coralline hydroxyapatite bone graft substitutes as an alternative to autogenous grafting in the clinical setting and emphasize the potential role of noninvasive densitometric techniques in monitoring the incorporation of bone-graft materials.

Porous hydroxyapatite as a bone graft substitute in diaphyseal defects: a histometric study.

Porous hydroxyapatite (IP200), formed by conversion of the Poritidae porites exoskeleton, has pores averaging 230 microns and pore interconnections averaging 190 microns in diameter. In the distal radial diaphyses of 14 dogs, bilateral 7.5 X 20 mm cortical windows were created and fitted with 5 X 7.5 X 20 mm blocks of IP200 implants and iliac autografts. Both implanted and contralateral grafted radius specimens were retrieved at 3, 6, 12, 24, and 48 months. Unstained undecalcified sections were examined by microradiography and UV epi-illumination. Stained undecalcified sections were examined by light microscopy and quantitated by histometric methods. Implant specimens demonstrated good union and bone ingrowth at all time intervals. The implant specimens were composed of (mean +/- SE) 10.6% +/- 1.0% soft tissue, 51.2% +/- 1.3% bone, and 38.2% +/- 1.0% IP200. The graft specimens showed good union with little apparent ingrowth at 3 months, followed by progressive appositional closure of cancellous spaces. The graft specimens contained 21.9% +/- 0.9% bone at 3 months with increases at each time interval to 73.1% +/- 8.7% at 48 months. The volume fraction and mean width of IP200 did not change with time, confirming the absence of implant biodegradation. The volume fraction and mean width of bone remained stable in the implant but increased in the graft specimens, corresponding to graft neocortex formation. It is concluded that implants initially filled in with bone while grafts initially replaced much of their spongiosa and subsequently filled in with bone. Histometry of untreated defects and measurement of mechanical properties are suggested for further study.

Development of a variable stiffness external fixation system for stabilization of segmental defects of the tibia.

The mechanical properties of a variable stiffness external fixation system were explored. Initial testing of a unilateral fixator configuration demonstrated that system rigidity could be increased by maximizing pin separation distance in the fracture component and the number of pins used while minimizing pin separation distance across the fracture site and the sidebar offset distance from bone. A triangulated system composed of half pin frames mounted anteriorly and medially on the tibial aspects and linked by crossbars was devised. Progressive disassembly of the frame was shown to result in progressive decreases in fixator rigidity in all planes.

Triple-technique (MR imaging, single-photon emission CT, and CT) coregistration for image-guided surgical evaluation of patients with intractable epilepsy.

Ictal and interictal single-photon emission CT (SPECT) play an increasingly important role in the surgical evaluation of patients with epilepsy. We present a method of coregistration of MR, SPECT, and CT images to correlate structural data (MR imaging), blood flow changes (SPECT), and location of subdural electrodes (CT) for patients undergoing image-guided surgical treatment of epilepsy. MR-SPECT root mean square (rms) mismatch distances were 2.1 to 2.5 mm, and MR-CT rms mismatch distances were 1.0 to 4.5 mm. Coregistration assisted in image-guided placement of subdural electrodes and in surgical resection of the suspected epileptogenic focus.

Endoscopic coagulation of the choroid plexus using the Nd:YAG laser: initial experience and proposal for management.

Although most patients with hydrocephalus are treated effectively with ventriculoperitoneal shunts, a small group fails to respond to diversion procedures. In some patients within this group, hydrocephalus may be caused in part by the overproduction of the cerebrospinal fluid (CSF). In other patients, previous shunt infections may limit the ability of the peritoneum to absorb fluid, and patient response to a ventriculoperitoneal shunt may be improved by reducing CSF production. We discuss a case of a 29-month-old hydrocephalic infant with a ventriculoperitoneal shunt who had ascites. Computed tomography showed bilateral symmetrical enlargement of the choroid plexus. Repeated cultures of the CSF and shunt tubing were sterile, and the daily production of the CSF exceeded 1000 ml. Therapy with acetazolamide decreased the CSF output temporarily, but it was discontinued after serious electrolyte abnormalities occurred. The endoscopic coagulation of the choroid plexus with a neodymium:YAG laser transmitted through a flexible quartz fiber decreased CSF production effectively. This procedure may be useful in a variety of clinical conditions associated with hydrocephalus or with other intraventricular lesions.

Magnetic source imaging: a review of the Magnes system of biomagnetic technologies incorporated.

Magnetic source imaging (MSI) is a new, noninvasive technique for defining the relationship between brain function and structure on a patient-to-patient basis. It achieves this by combining detailed neurophysiological data derived from magnetoencephalography with high-quality neuroanatomical data derived via magnetic resonance imaging. By the use of mathematical models, the spatial locations of those neurons that generate neuromagnetic signals of interest are estimated and subsequently marked on spatially aligned magnetic resonance images. There are three prominent types of clinical MSI examinations. These are: 1) functional mapping examinations in which sensory and motor functions are localized; 2) examinations of interictal epileptiform activity; and 3) examinations of abnormal low-frequency magnetic activity, which has been found to be present in a wide range of pathophysiological conditions. Functional mapping provides useful information regarding the relationship between the cortical representation of eloquent function and the location of pathological lesions that may be surgically resectable. This application is of particular utility in cases of intracortical masses that distort and obscure the local neuroanatomy. By defining the primary sites of interictal epileptiform activity, MSI examinations are useful in the surgical planning for the implantation of depth electrodes and the planning of partial lobectomies. Abnormal low-frequency magnetic activity appears to be a neurophysiological correlate of ischemic penumbra associated with stroke, neoplasms, and vascular malformations. Abnormal low-frequency magnetic activity has also been found to be present in several other conditions, including head trauma and psychiatric dysfunction, although the exact pathophysiological mechanisms are presently unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Halo vest versus spinal fusion for cervical injury: evidence from an outcome study.

The indications for surgical fusion, as opposed to halo fixation, in the management of cervical spine injury are still unclear. At St. Louis University Medical Center a conservative protocol has been adopted to treat almost all cervical spine fractures with halo fixation. To determine what factors have contributed to failure of halo fixation, the records and radiographs of all patients with cervical spine injuries who were treated at that institution between 1984 and 1986 were reviewed. During this interval, 124 patients were treated, consisting of 93 men and 31 women between 6 and 94 years old. Of these, 15 (12%) had cervical fusion without preoperative halo device application. This group included eight patients with old injuries and delayed diagnosis, three with nonreducible locked facets, and four with miscellaneous indications. The remaining 109 patients were treated with halo vests. Four died before completing the 3-month standard treatment. Of those completing the treatment, 48 had C1-2 level injuries and 57 had C3-T1 level injuries. Sixteen patients (15%) failed their halo treatments and required surgical fusion: eight while still in halo fixation and eight after they had completed treatment with a halo device. Failure of halo treatment was indicated by recurrent dislocation in 13 patients and increased neurological deficit in three. Thirteen of the patients who failed treatment had C3-T1 injuries and three had C1-2 injuries. Of 27 patients with odontoid fractures, only two (7.4%) failed halo fixation. There were no failures in 11 patients with hangman's fractures. Of the 57 patients with C3-T1 injuries, 13 (23%) failed treatment, nine of whom had locked or "perched" facets. The factors causing failure of halo fixation were analyzed. The overall success rate was 85%, suggesting that the halo vest can be used to treat most patients with cervical spine injuries. Under certain circumstances (in the presence of old injuries, difficult reduction, or locked or "perched" facets), surgery may be indicated to avoid unnecessary delay in definitive management.

Evoked somatosensory potentials to common peroneal nerve stimulation in man.

This study was undertaken to identify the normal somatosensory evoked potential pattern from stimulation of the common peroneal nerve in order to provide basic data for clinical use in diagnosis and management of patients with spinal cord lesions. Thirty-four adult volunteers, free of neurological disease, and 12 patients were tested. The recording technique is described and is similar to that reported by Perot. The primary evoked response (P1) was easily visualized in 88% of the recordings from normal subjects. The peak latency of the primary response was 38.9 msec, and the deflection was positive. A vertex potential (P4) was a relatively consistent peak that appeared at approximately 240 msec in 78% of the subjects. Additional components of the waveform are also described and are compared to previous studies. Clinically, the presence of primary response seems to correlate with a favorable neurological outcome, and recovery of the primary response may precede major clinical improvement. The literature is reviewed and results compared to the current study.

Variables affecting the accuracy of stereotactic localization using computerized tomography.

Stereotactic localization using computerized tomography (CT) is increasingly employed to guide neurosurgical procedures in crucial areas of the brain such as the brain stem. This technique allows the surgeon to resect a lesion in its entirety while sparing critical areas of the brain. Thus, the parameters used for scanning should be selected for maximum accuracy. While the small pixel size of CT scanners suggests a high degree of precision in localization, there have been few systematic studies of this accuracy. The authors have studied the amount of error in localization created by variables such as CT scan thickness, interscan spacing, size of lesion, and method of computation when using the Brown-Roberts-Wells (BRW) stereotactic system. Over 1000 CT scans were made of a phantom composed of spheres of differing diameter and location. The CT slice thickness was varied from 1.5 to 5.0 mm, and interscan spacing was varied from 0.5 to 3.0 mm. The coordinates of the center of the spheres were calculated independently using the laptop computer supplied with the unit and also by a stereotactic computer which automatically calculates the center of the fiducials. The actual BRW coordinates of the sphere center were obtained using the phantom base and were then compared to the computer-calculated coordinates to determine error in localization. Variables with a significant effect on error included the scan thickness, interscan spacing, and sphere size. The mean error decreased 23% as the scan thickness decreased from 5.0 to 1.5 mm and 45% as the interscan spacing decreased from 3.0 to 0.5 mm. Mean error was greatest for the smallest sphere sizes. The two computational methods did not differ in error. This study suggests that, for critical areas of the brain or for small lesions, a scan thickness of 1.5 mm and interscan spacing of 0.5 mm should be employed.

Spinal cord arteriovenous malformation with an associated lymphatic anomaly. Case report.

Spinal cord arteriovenous malformations (AVM's), like other vascular anomalies of the central nervous system, can be associated with similar vascular lesions of the skin and viscera. A 7-year-old girl, who presented with rapidly progressing paraplegia, was found to have a spinal cord AVM, cutaneous angioma, and a chylous malformation of the lymphatic system. She had previously undergone treatment for a posterior thoracic cutaneous angioma. At surgery, upon incision of the paravertebral muscle fascia, viscous pale fluid was encountered emanating from a foramen in the thoracic lamina. The spinal AVM was resected in spite of concern that the abnormality represented spinal osteomyelitis. Postoperatively, there was full return of function in the lower extremities, along with recurrent episodes of chylothorax, which slowly came under control with dietary manipulation. A review of the anatomy of the thoracic duct and nontraumatic causes of chylothorax is presented, and the association of cutaneous and central angiomas is discussed. Finally, the treatment of chylothorax is delineated.

Temporoparietal craniopagus. Case report and review of the literature.

A case of craniopagus twins joined in the temporoparietal area is presented, along with a review of the literature on craniopagus. A large area of brain was shared between the neurologically normal infants, with defects in the scalp, skull, and dura. The twins were separated in a three-step procedure. First, areas of shared brain were divided and separated with silicone sheets. The second procedure consisted of the insertion of scalp expanders to allow primary skin closure. In the third procedure complete separation was performed which was complicated by severe hypotension in one infant that was due to dural sinus hemorrhage. Cerebrospinal fluid leak was the most difficult problem encountered in the postoperative period; this was treated with lumboperitoneal and ventriculoperitoneal shunts. After 2 years, one twin is neurologically normal; the other is severely developmentally delayed, possibly related to the severe hypotension experienced during the third procedure. A review of the literature on craniopagus is presented. Analysis of data in the literature suggests that the area involved in the craniopagus as well as the venous connections are closely related to survival following separation of craniopagus twins.

Presurgical localization of functional cortex using magnetic source imaging.

The boundaries of somatosensory cortex were localized noninvasively by means of a large-array biomagnetometer in six patients with mass lesions in or near eloquent cortex. The results were used by neurosurgeons and neurologists in preoperative planning and for reference in the operating room. The magnetic source imaging (MSI) localizations from somatosensory evoked potentials were used to predict the pattern of phase reversals measurable intraoperatively on the cortical surface, providing a quantitative comparison between the two measures. The magnetic localizations were found to be predictive in all six cases, with the two sets of localizations falling within an 8-mm distance on average. Somatosensory localizations using MSI offer accuracy in localizing somatosensory cortex stereotactically and in depicting its relationship to lesions. Such data are valuable preoperatively in assessing the risks associated with a proposed surgical procedure and for optimizing subsequent minimum-risk surgical strategy.

The pathological anatomy of Malgaigne fracture-dislocations of the pelvis.

Despite renewed interest in the reduction and external fixation of pelvic disruptions, anatomical studies of such injuries are lacking. Of 150 consecutive victims of multiple trauma examined at autopsy, forty-seven (31 per cent) were found to have a pelvic injury. Twenty-six of the thirty-two cadavera that were examined radiographically and dissected had a double break in the pelvic ring (Malgaigne pattern). An anatomical classification based on the degree of posterior injury to the ring is proposed. Anatomical reduction of the posterior fracture-dislocation by external manipulation was impossible in the majority of cadavera because of either ligamentous or osseous interposition, or both, in the sacro-iliac joint, or because of triplane displacement of the hemipelvis.

The role of computerized tomographic scanning in the evaluation of major pelvic fractures.

Twenty-five patients with double vertical fractures of the pelvic ring had evaluations by both plain radiography and computed-tomography scanning of the pelvis. In eight of the twenty-five patients, the interpretation that was made from the plain radiographs, based on the classification of Pennal et al., changed when additional anatomical information was provided by the computed-tomography scan. We recommend that computed tomography be used for: (1) double vertical fracture-dislocations of the pelvic ring in which plain radiographs are inadequate to judge pelvic stability, (2) fractures of the pelvic ring with extension into the acetabulum, and (3) major injuries to the hemipelvis that are to be treated by open reduction and internal fixation. However, due to the increased cost and radiation exposure, routine computed-tomography scanning is not justified for all injuries to the pelvic ring.

The pathological anatomy of fatal atlanto-occipital dislocations.

Nine atlanto-occipital dislocations were found in postmortem examinations of 112 victims of multiple trauma. Axial traction facilitated roentgenographic identification of the injury. A hyperextension mechanism of injury was suggested by the associated injuries, including submental lacerations and mandibular fractures. Atlanto-occipital dislocations were more frequent in children than in adults. A pure dislocation injury without fracture was identified.