The Minnesota Multiphasic Personality Inventory-2-RF in Treatment-Seeking Veterans with History of Mild Traumatic Brain Injury.

OBJECTIVE: This study examined the Minnesota Multiphasic Personality Inventory-Second Edition-Restructured Form (MMPI-2-RF) to better understand symptom presentation in a sample of treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with self-reported history of mild traumatic brain injury (mTBI). METHOD: Participants underwent a comprehensive clinical neuropsychological battery including performance and symptom validity measures and self-report measures of depressive, posttraumatic, and post-concussive symptomatology. Those with possible symptom exaggeration (SE+) on the MMPI-2-RF were compared with those without (SE-) with regard to injury, psychiatric, validity, and cognitive variables. RESULTS: Between 50% and 87% of participants demonstrated possible symptom exaggeration on one or more MMPI-2-RF validity scales, and a large majority were elevated on content scales related to cognitive, somatic, and emotional complaints. The SE+ group reported higher depressive, posttraumatic, and post-concussive symptomatology, had higher scores on symptom validity measures, and performed more poorly on neuropsychological measures compared with the SE- group. There were no group differences with regard to injury variables or performance validity measures. Participants were more likely to exhibit possible symptom exaggeration on cognitive/somatic compared with traditional psychopathological validity scales. CONCLUSIONS: A sizable portion of treatment-seeking OEF/OIF Veterans demonstrated possible symptom exaggeration on MMPI-2-RF validity scales, which was associated with elevated scores on self-report measures and poorer cognitive performance, but not higher rates of performance validity failure, suggesting symptom and performance validity are distinct concepts. These findings have implications for the interpretation of clinical data in the context of possible symptom exaggeration and treatment in Veterans with persistent post-concussive symptoms.

A line fiducial method for geometric calibration of cone-beam CT systems with diverse scan trajectories.

Modern cone-beam CT systems, especially C-arms, are capable of diverse source-detector orbits. However, geometric calibration of these systems using conventional configurations of spherical fiducials (BBs) may be challenged for novel source-detector orbits and system geometries. In part, this is because the BB configurations are designed with careful forethought regarding the intended orbit so that BB marker projections do not overlap in projection views. Examples include helical arrangements of BBs (Rougee et al 1993 Proc. SPIE 1897 161-9) such that markers do not overlap in projections acquired from a circular orbit and circular arrangements of BBs (Cho et al 2005 Med. Phys. 32 968-83). As a more general alternative, this work proposes a calibration method based on an array of line-shaped, radio-opaque wire segments. With this method, geometric parameter estimation is accomplished by relating the 3D line equations representing the wires to the 2D line equations of their projections. The use of line fiducials simplifies many challenges with fiducial recognition and extraction in an orbit-independent manner. For example, their projections can overlap only mildly, for any gantry pose, as long as the wires are mutually non-coplanar in 3D. The method was tested in application to circular and non-circular trajectories in simulation and in real orbits executed using a mobile C-arm prototype for cone-beam CT. Results indicated high calibration accuracy, as measured by forward and backprojection/triangulation error metrics. Triangulation errors on the order of microns and backprojected ray deviations uniformly less than 0.2 mm were observed in both real and simulated orbits. Mean forward projection errors less than 0.1 mm were observed in a comprehensive sweep of different C-arm gantry angulations. Finally, successful integration of the method into a CT imaging chain was demonstrated in head phantom scans.

Geometric Calibration Using Line Fiducials for Cone-Beam CT with General, Non-Circular Source-Detector Trajectories.

PURPOSE: Traditional BB-based geometric calibration methods for cone-beam CT (CBCT) rely strongly on foreknowledge of the scan trajectory shape. This is a hindrance to the implementation of variable trajectory CBCT systems, normally requiring a dedicated calibration phantom or software algorithm for every scan orbit of interest. A more flexible method of calibration is proposed here that accommodates multiple orbit types - including strongly noncircular trajectories - with a single phantom and software routine. METHODS: The proposed method uses a calibration phantom consisting of multiple line-shaped wire segments. Geometric models relating the 3D line equations of the wires to the 2D line equations of their projections are used as the basis for system geometry estimation. This method was tested using a mobile C-arm CT system and comparisons were made to standard BB-based calibrations. Simulation studies were also conducted using a sinusoid-on-sphere orbit. Calibration performance was quantified in terms of Point Spread Function (PSF) width and back projection error. Visual image quality was assessed with respect to spatial resolution in trabecular bone in an anthropomorphic head phantom. RESULTS: The wire-based calibration method performed equal to or better than BB-based calibrations in all evaluated metrics. For the sinusoidal scans, the method provided reliable calibration, validating its application to non-circular trajectories. Furthermore, the ability to improve image quality using non-circular orbits in conjunction with this calibration method was demonstrated. CONCLUSION: The proposed method has been shown feasible for conventional circular CBCT scans and offers a promising tool for non-circular scan orbits that can improve image quality, reduce dose, and extend field of view.

Multi-stage 3D-2D registration for correction of anatomical deformation in image-guided spine surgery.

A multi-stage image-based 3D-2D registration method is presented that maps annotations in a 3D image (e.g. point labels annotating individual vertebrae in preoperative CT) to an intraoperative radiograph in which the patient has undergone non-rigid anatomical deformation due to changes in patient positioning or due to the intervention itself. The proposed method (termed msLevelCheck) extends a previous rigid registration solution (LevelCheck) to provide an accurate mapping of vertebral labels in the presence of spinal deformation. The method employs a multi-stage series of rigid 3D-2D registrations performed on sets of automatically determined and increasingly localized sub-images, with the final stage achieving a rigid mapping for each label to yield a locally rigid yet globally deformable solution. The method was evaluated first in a phantom study in which a CT image of the spine was acquired followed by a series of 7 mobile radiographs with increasing degree of deformation applied. Second, the method was validated using a clinical data set of patients exhibiting strong spinal deformation during thoracolumbar spine surgery. Registration accuracy was assessed using projection distance error (PDE) and failure rate (PDE > 20 mm-i.e. label registered outside vertebra). The msLevelCheck method was able to register all vertebrae accurately for all cases of deformation in the phantom study, improving the maximum PDE of the rigid method from 22.4 mm to 3.9 mm. The clinical study demonstrated the feasibility of the approach in real patient data by accurately registering all vertebral labels in each case, eliminating all instances of failure encountered in the conventional rigid method. The multi-stage approach demonstrated accurate mapping of vertebral labels in the presence of strong spinal deformation. The msLevelCheck method maintains other advantageous aspects of the original LevelCheck method (e.g. compatibility with standard clinical workflow, large capture range, and robustness against mismatch in image content) and extends capability to cases exhibiting strong changes in spinal curvature.

Intraoperative evaluation of device placement in spine surgery using known-component 3D-2D image registration.

Intraoperative x-ray radiography/fluoroscopy is commonly used to assess the placement of surgical devices in the operating room (e.g. spine pedicle screws), but qualitative interpretation can fail to reliably detect suboptimal delivery and/or breach of adjacent critical structures. We present a 3D-2D image registration method wherein intraoperative radiographs are leveraged in combination with prior knowledge of the patient and surgical components for quantitative assessment of device placement and more rigorous quality assurance (QA) of the surgical product. The algorithm is based on known-component registration (KC-Reg) in which patient-specific preoperative CT and parametric component models are used. The registration performs optimization of gradient similarity, removes the need for offline geometric calibration of the C-arm, and simultaneously solves for multiple component bodies, thereby allowing QA in a single step (e.g. spinal construct with 4-20 screws). Performance was tested in a spine phantom, and first clinical results are reported for QA of transpedicle screws delivered in a patient undergoing thoracolumbar spine surgery. Simultaneous registration of ten pedicle screws (five contralateral pairs) demonstrated mean target registration error (TRE) of 1.1 ± 0.1 mm at the screw tip and 0.7 ± 0.4° in angulation when a prior geometric calibration was used. The calibration-free formulation, with the aid of component collision constraints, achieved TRE of 1.4 ± 0.6 mm. In all cases, a statistically significant improvement (p < 0.05) was observed for the simultaneous solutions in comparison to previously reported sequential solution of individual components. Initial application in clinical data in spine surgery demonstrated TRE of 2.7 ± 2.6 mm and 1.5 ± 0.8°. The KC-Reg algorithm offers an independent check and quantitative QA of the surgical product using radiographic/fluoroscopic views acquired within standard OR workflow. Such intraoperative assessment could improve quality and safety, provide the opportunity to revise suboptimal constructs in the OR, and reduce the frequency of revision surgery.

Registration of MRI to intraoperative radiographs for target localization in spinal interventions.

Decision support to assist in target vertebra localization could provide a useful aid to safe and effective spine surgery. Previous solutions have shown 3D-2D registration of preoperative CT to intraoperative radiographs to reliably annotate vertebral labels for assistance during level localization. We present an algorithm (referred to as MR-LevelCheck) to perform 3D-2D registration based on a preoperative MRI to accommodate the increasingly common clinical scenario in which MRI is used instead of CT for preoperative planning. Straightforward adaptation of gradient/intensity-based methods appropriate to CT-to-radiograph registration is confounded by large mismatch and noncorrespondence in image intensity between MRI and radiographs. The proposed method overcomes such challenges with a simple vertebrae segmentation step using vertebra centroids as seed points (automatically defined within existing workflow). Forwards projections are computed using segmented MRI and registered to radiographs via gradient orientation (GO) similarity and the CMA-ES (covariance-matrix-adaptation evolutionary-strategy) optimizer. The method was tested in an IRB-approved study involving 10 patients undergoing cervical, thoracic, or lumbar spine surgery following preoperative MRI. The method successfully registered each preoperative MRI to intraoperative radiographs and maintained desirable properties of robustness against image content mismatch and large capture range. Robust registration performance was achieved with projection distance error (PDE) (median ± IQR) = 4.3 ± 2.6 mm (median ± IQR) and 0% failure rate. Segmentation accuracy for the continuous max-flow method yielded dice coefficient = 88.1 ± 5.2, accuracy = 90.6 ± 5.7, RMSE = 1.8 ± 0.6 mm, and contour affinity ratio (CAR) = 0.82 ± 0.08. Registration performance was found to be robust for segmentation methods exhibiting RMSE <3 mm and CAR >0.50. The MR-LevelCheck method provides a potentially valuable extension to a previously developed decision support tool for spine surgery target localization by extending its utility to preoperative MRI while maintaining characteristics of accuracy and robustness.

Deformable 3D-2D Registration of Known Components for Image Guidance in Spine Surgery.

A 3D-2D image registration method is reported for guiding the placement of surgical devices (e.g., K-wires). The solution registers preoperative CT (and planning data therein) to intraoperative radiographs and computes the pose, shape, and deformation parameters of devices (termed "components") known to be in the radiographic scene. The deformable known-component registration (dKC-Reg) method was applied in experiments emulating spine surgery to register devices (K-wires and spinal fixation rods) undergoing realistic deformation. A two-stage registration process (i) resolves patient pose from individual radiographs and (ii) registers components represented as polygonal meshes based on a B-spline model. The registration result can be visualized as overlay of the component in CT analogous to surgical navigation but without conventional trackers or fiducials. Target registration error in the tip and orientation of deformable K-wires was (1.5±0.9)mm and 0.6∘±0.2∘, respectively. For spinal fixation rods, the registered components achieved Hausdorff distance of 3.4 mm. Future work includes testing in cadaver and clinical data and extension to more generalized deformation and component models.

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Rate and correlates of weight change in Huntington's disease.

OBJECTIVE: To determine the rate and correlates of weight change in a large, well characterised sample of patients with Huntington's disease followed at 44 sites by the Huntington Study Group. PARTICIPANTS AND METHODS: Weight change was assessed in 927 adults with a definite diagnosis of Huntington's disease who were followed prospectively for (mean (SD)) 3.4 (1.4) years. The unified Huntington's disease rating scale was used to assess weight, motor dysfunction (including chorea and dystonia), depressive symptoms, and functional decline. RESULTS: Random effects modelling determined that patients gained an average of 0.11 (1.7) kg/year and their chorea scores increased by 0.36 (0.78) points/year. There were significant but weak relations between weight loss and increasingly severe chorea (r = -0.13), worse baseline motor performance (r = -0.12), less severe baseline depressed mood (r = 0.14), and poorer baseline independence ratings (r = 0.07). Patients who were within 0 to 2 years of symptom onset at the time of the baseline visit gained more weight than those with longer disease duration. CONCLUSIONS: Weight loss following symptom onset is not a consistent feature of Huntington's disease. The mechanisms contributing to weight change in this condition are unclear and probably multifactorial. Future studies examining asymptomatic carriers of the mutation could be helpful in identifying incipience of low body weight and may be better suited for identifying clinical correlates of weight loss than studies in symptomatic patients.

Behavioural abnormalities contribute to functional decline in Huntington's disease.

The independent and relative contributions of motor, cognitive, and behavioural deficits to functional decline in patients with Huntington's disease are examined. Twenty two patients with Huntington's disease were assessed with rating scales for motor dysfunction, cognitive measures of executive functions, and behavioural measures of apathy, executive dysfunction, and disinhibition. Their functional status was assessed with informant based and clinician based ratings of activities of daily living (ADL). A composite apathy/executive dysfunction behavioural index was strongly related to decline in ADL independently and after controlling for motor and cognitive deficits. These results suggest that behavioural dysfunction contributes to functional decline in patients with Huntington's disease and may impede their ability to utilise motor or cognitive skills that remain available in the early stages of the disease.

Biomedical publishing and the internet: evolution or revolution?

The Internet is challenging traditional publishing patterns. In the biomedical domain, medical journals are providing more and more content online, both free and for a fee. Beyond this, however, a number of commentators believe that traditional notions of copyright and intellectual property ownership are no longer suited to the information age and that ownership of copyright to research reports should be and will be wrested from publishers and returned to authors. In this paper, it is argued that, although the Internet will indeed profoundly affect the distribution of biomedical research results, the biomedical publishing industry is too intertwined with the research establishment and too powerful to fall prey to such a copyright revolution.

Neuropsychological deficits associated with antiphospholipid antibodies.

Neurologic events associated with antiphospholipid antibodies (aPAs) include transient ischemic attack, stroke, and vascular dementia in individuals much younger than is typically observed with these disorders. The present study evaluated 27 non-elderly adults with aPAs but without concurrent disease processes or history of neurologic event and 27 age- and education-matched controls. MANOVA (p <.01) indicated group differences in executive functioning, verbal learning and memory, and visuospatial ability. In contrast, gross attentional processes and fine motor skills appeared unaffected by the syndrome. Moreover, the frequency of impaired neuropsychologic performance was greater among individuals with aPAs than among controls (p <.01). The presence of cognitive deficits in otherwise asymptomatic patients with aPAs indicates a preclinical phase of neurologic involvement and may prove to be the most sensitive markers of the syndrome.

The effect on memory of chronic prednisone treatment in patients with systemic disease.

There have been no systematic investigations of the effects of glucocorticoid treatment on memory in a clinical population despite experimental and clinical evidence that such treatment could cause memory disturbance. We conducted both cross-sectional and longitudinal studies. In Study 1, we administered tests of both hippocampal-dependent explicit memory and hippocampal-independent implicit memory to twenty-five prednisone-treated patients with systemic disease without CNS involvement and 25 matched clinical controls. All treated patients were taking doses of 5 to 40 mg of prednisone daily for at least 1 year. The glucocorticoid-treated group performed worse than the controls on tests of explicit memory, but the groups did not differ on the implicit memory task. Multiple regression analyses suggested that elderly patients are more susceptible to memory impairment with less protracted treatment. The results of Study 2, a prospective, longitudinal study of the effects of prednisone on memory across 3 months of therapy, suggest that even acute treatment can adversely affect memory. The observed alteration in memory was not secondary to inattention, affective disturbance, generalized global cognitive decline, or severity of disease. Results reported here, combined with previous clinical and experimental reports, indicate that the risk of memory impairment should be carefully considered before initiating treatment with glucocorticoids. Conversely, use of glucocorticoids should be considered in the differential diagnosis of memory loss. Finally, the potential benefit of anti-inflammatory treatment in Alzheimer's disease might be counterbalanced by possible iatrogenic memory impairment, at least when synthetic glucocorticoids are considered.

A review of neurological sequelae and cognitive deficits associated with antiphospholipid antibodies.

Antiphospholipid Antibodies (aPAs) are specific circulating immunoglobulins that lead to a hypercoagulant state and recurrent arterial and venous thromboembolic events. The cerebral circulation is the most common site of arterial occlusion in aPAs, and neurologic events include amaurosis fugax, migrainous cephalalgia, transient ischemic attacks (TIA), stroke, ischemic encephalopathy, and vascular dementia. A review of the literature yields numerous studies citing neurocognitive and neuropsychiatric symptoms associated with this syndrome in a much younger population than is seen in other cerebrovascular disorders. These associated features include focal and generalized cognitive deficits, early-onset vascular dementia, and neuropsychiatric symptoms such as affective and thought disorders. These neurocognitive and neurobehavioral manifestations may be underemphasized in this population and aPAs should be considered in a differential diagnosis. Largescale prospective studies are needed to quantify psychiatric and neuropsychological sequelae of this disorder.

Visuoperceptual-spatial ability and visual memory in vascular dementia and dementia of the Alzheimer type.

This study investigated the relationship between visuoperceptual ability and visual memory in dementia. Twenty individuals with probable dementia of the Alzheimer type, 24 individuals with probable vascular dementia, and 20 healthy, elderly adults underwent neuropsychological evaluation. Hierarchical multiple regression analyses suggested that perceptual organization skills contributed to a significant amount of the variance in novel, but not famous, face recognition. This finding was most robust in the clinical groups. Causality cannot be attributed from this regression model. Results suggest, however, that visual processing deficits are more strongly related to the memory process at the time of encoding rather than during recognition of remote information.

Selective activation of human suppressor cells by a nonproliferative stimulus.

The eliciting of suppressor cell activity by heat-treated stimulating cells demonstrates that suppression can be induced by an antigenic but non-effective mixed lymphocyte culture (MLC) stimulus in vitro. Simultaneous or prior MLC or cytotoxic T lymphocyte activity is not required for alloantigen-induced suppressor cell activation.