Dynamic registration using ultrasound for anatomical referencing

This paper proposes methods to circumvent the need to attach physical markers to bones for anatomical referencing in computer-assisted orthopedic surgery. Using ultrasound, a bone could be non-invasively referenced, and so the problem is formulated as the need for dynamic registration. A method for correspondence establishment is presented, and the matching step is based on three least-squares algorithms: two that are typically used in registration methods such as ICP, and the third is a form of the Unscented Kalman filter that was adapted to work in this context. A simulation was developed in order to reliably evaluate and compare the dynamic registration methods

Statistical shape analysis via principal factor analysis

Statistical shape analysis techniques commonly employed in the medical imaging community, such as active shape models or active appearance models, rely on principal component analysis (PCA) to decompose shape variability into a reduced set of interpretable components. In this paper we propose principal factor analysis (PFA) as an alternative and complementary tool to PCA providing a decomposition into modes of variation that can be more easily interpretable, while still being a linear efficient technique that performs dimensionality reduction (as opposed to independent component analysis, ICA). The key difference between PFA and PCA is that PFA models covariance between variables, rather than the total variance in the data. The added value of PFA is illustrated on 2D landmark data of corpora callosa outlines. Then, a study of the 3D shape variability of the human left femur is performed. Finally, we report results on vector-valued 3D deformation fields resulting from non-rigid registration of ventricles in MRI of the brain.

Correspondence establishment in statistical modeling of shapes with arbitrary topology

Correspondence establishment is a key step in statistical shape model building. There are several automated methods for solving this problem in 3D, but they usually can only handle objects with simple topology, like that of a sphere or a disc. We propose an extension to correspondence establishment over a population based on the optimization of the minimal description length function, allowing considering objects with arbitrary topology. Instead of using a fixed structure of kernel placement on a sphere for the systematic manipulation of point landmark positions, we rely on an adaptive, hierarchical organization of surface patches. This hierarchy can be built on surfaces of arbitrary topology and the resulting patches are used as a basis for a consistent, multi-scale modification of the surfaces' parameterization, based on point distribution models. The feasibility of the approach is demonstrated on synthetic models with different topologies.

Hardware accelerated ray cast of volume data and volume gradient for an optimized splines-based multi-resolution 2D-3D registration

This paper describes a method for DRR generation as well as for volume gradients projection using hardware accelerated 2D texture mapping and accumulation buffering and demonstrates its application in 2D-3D registration of X-ray fluoroscopy to CT images. The robustness of the present registration scheme are guaranteed by taking advantage of a coarse-to-fine processing of the volume/image pyramids based on cubic B-splines. A human cadaveric spine specimen together with its ground truth was used to compare the present scheme with a purely software-based scheme in three aspects: accuracy, speed, and capture ranges. Our experiments revealed an equivalent accuracy and capture ranges but with much shorter registration time with the present scheme. More specifically, the results showed 0.8 mm average target registration error, 55 second average execution time per registration, and 10 mm and 10° capture ranges for the present scheme when tested on a 3.0 GHz Pentium 4 computer.

Non-photorealistic rendering of virtual implant models for computer-assisted fluoroscopy-based surgical procedures

Surgical navigation systems visualize the positions and orientations of surgical instruments and implants as graphical overlays onto a medical image of the operated anatomy on a computer monitor. The orthopaedic surgical navigation systems could be categorized according to the image modalities that are used for the visualization of surgical action. In the so-called CT-based systems or 'surgeon-defined anatomy' based systems, where a 3D volume or surface representation of the operated anatomy could be constructed from the preoperatively acquired tomographic data or through intraoperatively digitized anatomy landmarks, a photorealistic rendering of the surgical action has been identified to greatly improve usability of these navigation systems. However, this may not hold true when the virtual representation of surgical instruments and implants is superimposed onto 2D projection images in a fluoroscopy-based navigation system due to the so-called image occlusion problem. Image occlusion occurs when the field of view of the fluoroscopic image is occupied by the virtual representation of surgical implants or instruments. In these situations, the surgeon may miss part of the image details, even if transparency and/or wire-frame rendering is used. In this paper, we propose to use non-photorealistic rendering to overcome this difficulty. Laboratory testing results on foamed plastic bones during various computer-assisted fluoroscopybased surgical procedures including total hip arthroplasty and long bone fracture reduction and osteosynthesis are shown.

Unifying energy minimization and mutual information maximization for robust 2D/3D registration of X-ray and CT images

Similarity measure is one of the main factors that affect the accuracy of intensity-based 2D/3D registration of X-ray fluoroscopy to CT images. Information theory has been used to derive similarity measure for image registration leading to the introduction of mutual information, an accurate similarity measure for multi-modal and mono-modal image registration tasks. However, it is known that the standard mutual information measure only takes intensity values into account without considering spatial information and its robustness is questionable. Previous attempt to incorporate spatial information into mutual information either requires computing the entropy of higher dimensional probability distributions, or is not robust to outliers. In this paper, we show how to incorporate spatial information into mutual information without suffering from these problems. Using a variational approximation derived from the Kullback-Leibler bound, spatial information can be effectively incorporated into mutual information via energy minimization. The resulting similarity measure has a least-squares form and can be effectively minimized by a multi-resolution Levenberg-Marquardt optimizer. Experimental results are presented on datasets of two applications: (a) intra-operative patient pose estimation from a few (e.g. 2) calibrated fluoroscopic images, and (b) post-operative cup alignment estimation from single X-ray radiograph with gonadal shielding.

Precise pose recovery of distal locking holes from single calibrated fluoroscopic image via a novel variable decomposition approach

This paper presents a novel variable decomposition approach for pose recovery of the distal locking holes using single calibrated fluoroscopic image. The problem is formulated as a model-based optimal fitting process, where the control variables are decomposed into two sets: (a) the angle between the nail axis and its projection on the imaging plane, and (b) the translation and rotation of the geometrical model of the distal locking hole around the nail axis. By using an iterative algorithm to find the optimal values of the latter set of variables for any given value of the former variable, we reduce the multiple-dimensional model-based optimal fitting problem to a one-dimensional search along a finite interval. We report the results of our in vitro experiments, which demonstrate that the accuracy of our approach is adequate for successful distal locking of intramedullary nails.

Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats

BACKGROUND: Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (RO 25-6981). Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28) or 3.75 mg (150 mg/kg; n = 15) every 3 h or an equal volume of sterile saline (250 microl; n = 40) starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus. RESULTS: Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P < 0.05 for all RO 25-6981 treated animals combined). The extent of apoptosis was not affected by low or high doses of RO 25-6981. Number of apoptotic cells (median [range]) was 12.76 [3.16-25.3] in animals treated with low dose RO 25-6981 (control animals 13.8 [2.60-31.8]; (P = NS) and 9.8 [1.7-27.3] (controls: 10.5 [2.4-21.75]) in animals treated with high dose RO 25-6981 (P = NS). CONCLUSIONS: Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures.

Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis

Matrix metalloproteinases (MMPs) and tumour necrosis factor alpha (TNF-alpha) converting enzyme (TACE) contribute synergistically to the pathophysiology of bacterial meningitis. TACE proteolytically releases several cell-surface proteins, including the proinflammatory cytokine TNF-alpha and its receptors. TNF-alpha in turn stimulates cells to produce active MMPs, which facilitate leucocyte extravasation and brain oedema by degradation of extracellular matrix components. In the present time-course studies of pneumococcal meningitis in infant rats, MMP-8 and -9 were 100- to 1000-fold transcriptionally upregulated, both in CSF cells and in brain tissue. Concentrations of TNF-alpha and MMP-9 in CSF peaked 12 h after infection and were closely correlated. Treatment with BB-1101 (15 mg/kg subcutaneously, twice daily), a hydroxamic acid-based inhibitor of MMP and TACE, downregulated the CSF concentration of TNF-alpha and decreased the incidences of seizures and mortality. Therapy with BB-1101, together with antibiotics, attenuated neuronal necrosis in the cortex and apoptosis in the hippocampus when given as a pretreatment at the time of infection and also when administration was started 18 h after infection. Functionally, the neuroprotective effect of BB-1101 preserved learning performance of rats assessed 3 weeks after the disease had been cured. Thus, combined inhibition of MMP and TACE offers a novel therapeutic strategy to prevent brain injury and neurological sequelae in bacterial meningitis.

Nitric oxide is protective in listeric meningoencephalitis of rats

The bacterium Listeria monocytogenes causes meningoencephalitis in humans. In rodents, listeriosis is associated with granulomatous lesions in the liver and the spleen, but not with meningoencephalitis. Here, infant rats were infected intracisternally to generate experimental listeric meningoencephalitis. Dose-dependent effects of intracisternal inoculation with L. monocytogenes on survival and activity were noted; 10(4) L. monocytogenes organisms induced a self-limiting brain infection. Bacteria invaded the basal meninges, chorioid plexus and ependyme, spread to subependymal tissue and hippocampus, and disappeared by day 7. This was paralleled by recruitment and subsequent disappearance of macrophages expressing inducible nitric oxide synthase (iNOS) and nitrotyrosine accumulation, an indication of nitric oxide (NO.) production. Treatment with the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) dramatically increased mortality and led to bacterial numbers in the brain 2 orders of magnitude higher than in control animals. Treatment with the selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) increased mortality to a similar extent and led to 1 order of magnitude higher bacterial counts in the brain, compared with controls. The numbers of bacteria that spread to the spleen and liver did not significantly differ among L-NIL-treated, PBN-treated, and control animals. Thus, the infant rat brain is able to mobilize powerful antilisterial mechanisms, and both reactive oxygen and NO. contribute to Listeria growth control.

The free radical scavenger alpha-phenyl-tert-butyl nitrone aggravates hippocampal apoptosis and learning deficits in experimental pneumococcal meningitis

The effect of adjuvant therapy with the radical scavenger alpha-phenyl-tert-butyl nitrone (PBN; 100 mg/kg given intraperitoneally every 8 h for 5 days) on brain injury and learning function was evaluated in an infant rat model of pneumococcal meningitis. Meningitis led to cortical necrotic injury (median, 3.97% [range, 0%-38.9%] of the cortex), which was reduced to a median of 0% (range, 0%-30.9%) of the cortex (P<.001) by PBN. However, neuronal apoptosis in the hippocampal dentate gyrus was increased by PBN, compared with that by saline (median score, 1.15 [range, 0.04-1.73] vs. 0.31 [range, 0-0.92]; P<.001). Learning function 3 weeks after cured infection, as assessed by the Morris water maze, was decreased, compared with that in uninfected control animals (P<.001). Parallel to the increase in hippocampal apoptosis, PBN further impaired learning in infected animals, compared with that in saline-treated animals (P<.02). These results contrast with those of an earlier study, in which PBN reduced cortical and hippocampal neuronal injury in group B streptococcal meningitis. Thus, in pneumococcal meningitis, antioxidant therapy with PBN aggravates hippocampal injury and learning deficits.

[In search of strategies for preventing brain damage as a sequela of bacterial meningitis]

Multiplication of bacteria within the central nervous system compartment triggers a host response with an overshooting inflammatory reaction which leads to brain parenchyma damage. Some of the inflammatory and neurotoxic mediators involved in the processes leading to neuronal injury during bacterial meningitis have been identified in recent years. As a result, the therapeutic approach to the disease has widened from eradication of the bacterial pathogen with antibiotics to attenuation of the detrimental effects of host defences. Corticosteroids represent an example of the adjuvant therapeutic strategies aimed at downmodulating excessive inflammation in the infected central nervous system. Pathophysiological concepts derived from an experimental rat model of bacterial meningitis revealed possible therapeutic strategies for prevention of brain damage. The insights gained led to the evaluation of new therapeutic modalities such as anticytokine agents, matrix metalloproteinase inhibitors, antioxidants, and antagonists of endothelin and glutamate. Bacterial meningitis is still associated with persistent neurological sequelae in approximately one third of surviving patients. Future research in the model will evaluate whether the neuroprotective agents identified so far have the potential to attenuate learning disabilities as a long-term consequence of bacterial meningitis.

Effects of clinically used antioxidants in experimental pneumococcal meningitis

Reactive oxygen intermediates mediate brain injury in bacterial meningitis. Several antioxidant drugs are clinically available, including N-acetylcysteine (NAC), deferoxamine (DFO), and trylizad-mesylate (TLM). The present study evaluated whether these antioxidants are beneficial in a model of pneumococcal meningitis. Eleven-day-old rats were infected intracisternally with Streptococcus pneumoniae and randomized to intraperitoneal treatment every 8 h with NAC (200 mg/kg), DFO (100 mg/kg), TLM (10 mg/kg), or saline (250 microL). TLM-treated animals showed a significantly reduced mortality compared with controls (P<.03). Meningitis led to extensive cortical injury at 22+/-2.2 h after infection (median, 14. 6% of cortex; range, 0-61.1%). Injury was significantly (P<.01) reduced to 1.1% (range, 0-34.6%) by NAC, to 2.3% (range, 0-19.6%) by DFO, and to 0.2% (range, 0-36.9%) by TLM (the difference was not significant among the 3 groups). None of the drugs reduced hippocampal injury. Thus, several clinically used antioxidants reduced cortical injury in experimental pneumococcal meningitis.