A statistical model of catheter motion from interventional x-ray images: application to image-based gating.

The motion and deformation of catheters that lie inside cardiac structures can provide valuable information about the motion of the heart. In this paper we describe the formation of a novel statistical model of the motion of a coronary sinus (CS) catheter based on principal component analysis of tracked electrode locations from standard mono-plane x-ray fluoroscopy images. We demonstrate the application of our model for the purposes of retrospective cardiac and respiratory gating of x-ray fluoroscopy images in normal dose x-ray fluoroscopy images, and demonstrate how a modification of the technique allows application to very low dose scenarios. We validated our method on ten mono-plane imaging sequences comprising a total of 610 frames from ten different patients undergoing radiofrequency ablation for the treatment of atrial fibrillation. For normal dose images we established systole, end-inspiration and end-expiration gating with success rates of 100%, 92.1% and 86.9%, respectively. For very low dose applications, the method was tested on the same ten mono-plane x-ray fluoroscopy sequences without noise and with added noise at signal to noise ratio (SNR) values of √50, √10, √8, √6, √5, √2 and √1 to simulate the image quality of increasingly lower dose x-ray images. The method was able to detect the CS catheter even in the lowest SNR images with median errors not exceeding 2.6 mm per electrode. Furthermore, gating success rates of 100%, 71.4% and 85.7% were achieved at the low SNR value of √2, representing a dose reduction of more than 25 times. Thus, the technique has the potential to extract useful information whilst substantially reducing the radiation exposure.

The effect of regularization in motion compensated PET image reconstruction: a realistic numerical 4D simulation study.

Following continuous improvement in PET spatial resolution, respiratory motion correction has become an important task. Two of the most common approaches that utilize all detected PET events to motion-correct PET data are the reconstruct-transform-average method (RTA) and motion-compensated image reconstruction (MCIR). In RTA, separate images are reconstructed for each respiratory frame, subsequently transformed to one reference frame and finally averaged to produce a motion-corrected image. In MCIR, the projection data from all frames are reconstructed by including motion information in the system matrix so that a motion-corrected image is reconstructed directly. Previous theoretical analyses have explained why MCIR is expected to outperform RTA. It has been suggested that MCIR creates less noise than RTA because the images for each separate respiratory frame will be severely affected by noise. However, recent investigations have shown that in the unregularized case RTA images can have fewer noise artefacts, while MCIR images are more quantitatively accurate but have the common salt-and-pepper noise. In this paper, we perform a realistic numerical 4D simulation study to compare the advantages gained by including regularization within reconstruction for RTA and MCIR, in particular using the median-root-prior incorporated in the ordered subsets maximum a posteriori one-step-late algorithm. In this investigation we have demonstrated that MCIR with proper regularization parameters reconstructs lesions with less bias and root mean square error and similar CNR and standard deviation to regularized RTA. This finding is reproducible for a variety of noise levels (25, 50, 100 million counts), lesion sizes (8 mm, 14 mm diameter) and iterations. Nevertheless, regularized RTA can also be a practical solution for motion compensation as a proper level of regularization reduces both bias and mean square error.

Respiratory motion models: a review.

The problem of respiratory motion has proved a serious obstacle in developing techniques to acquire images or guide interventions in abdominal and thoracic organs. Motion models offer a possible solution to these problems, and as a result the field of respiratory motion modelling has become an active one over the past 15 years. A motion model can be defined as a process that takes some surrogate data as input and produces a motion estimate as output. Many techniques have been proposed in the literature, differing in the data used to form the models, the type of model employed, how this model is computed, the type of surrogate data used as input to the model in order to make motion estimates and what form this output should take. In addition, a wide range of different application areas have been proposed. In this paper we summarise the state of the art in this important field and in the process highlight the key papers that have driven its advance. The intention is that this will serve as a timely review and comparison of the different techniques proposed to date and as a basis to inform future research in this area.

Temozolomide in the management of dopamine agonist-resistant prolactinomas.

BACKGROUND: The majority of prolactinomas respond to dopamine agonist therapy, but a proportion are resistant, requiring other treatments including surgery and/or radiotherapy. Temozolomide is an oral chemotherapy agent, which has been used as a salvage therapy to treat aggressive pituitary adenomas and carcinomas, including prolactinomas, unresponsive to all conventional treatment. CASE SERIES: We report three patients where temozolomide was used in the treatment of refractory prolactinomas. Case 1 describes a patient with a highly invasive prolactinoma, resistant to all conventional therapy, which responded dramatically to temozolomide used as a salvage treatment. In case 2, temozolomide was used after incomplete surgical resection to relieve chiasmal compression and avoid chiasm exposure to radiotherapy. In case 3, temozolomide enabled radiotherapy to be deferred in a 16-year old with a resistant prolactinoma. In all three cases, the tumours were negative by immunostaining for methylguanine methyltransferase (MGMT). LITERATURE REVIEW AND DISCUSSION: A review of the published literature reveals 51 reported cases of temozolomide treatment for pituitary tumours, including 20 prolactinomas. Fifteen of the 20 prolactinomas showed a good response to temozolomide. Our analysis demonstrates a strong association between MGMT-negative staining and a good response to temozolomide (OR 9.35, P = 0.0030). Current clinical practice is to use temozolomide as a salvage therapy after all conventional modalities of treatment have failed. We suggest that, in selected cases, consideration should be given to using temozolomide earlier in the treatment algorithm.

Nonrigid motion modeling of the liver from 3-D undersampled self-gated golden-radial phase encoded MRI.

Magnetic resonance imaging (MRI) has been commonly used for guiding and planning image guided interventions since it provides excellent soft tissue visualization of anatomy and allows motion modeling to predict the position of target tissues during the procedure. However, MRI-based motion modeling remains challenging due to the difficulty of acquiring multiple motion-free 3-D respiratory phases with adequate contrast and spatial resolution. Here, we propose a novel retrospective respiratory gating scheme from a 3-D undersampled high-resolution MRI acquisition combined with fast and robust image registrations to model the nonrigid deformation of the liver. The acquisition takes advantage of the recently introduced golden-radial phase encoding (G-RPE) trajectory. G-RPE is self-gated, i.e., the respiratory signal can be derived from the acquired data itself, and allows retrospective reconstructions of multiple respiratory phases at any arbitrary respiratory position. Nonrigid motion modeling is applied to predict the liver deformation of an average breathing cycle. The proposed approach was validated on 10 healthy volunteers. Motion model accuracy was assessed using similarity-, surface-, and landmark-based validation methods, demonstrating precise model predictions with an overall target registration error of TRE = 1.70 ± 0.94 mm which is within the range of the acquired resolution.

Thoracic respiratory motion estimation from MRI using a statistical model and a 2-D image navigator.

Respiratory motion models have potential application for estimating and correcting the effects of motion in a wide range of applications, for example in PET-MR imaging. Given that motion cycles caused by breathing are only approximately repeatable, an important quality of such models is their ability to capture and estimate the intra- and inter-cycle variability of the motion. In this paper we propose and describe a technique for free-form nonrigid respiratory motion correction in the thorax. Our model is based on a principal component analysis of the motion states encountered during different breathing patterns, and is formed from motion estimates made from dynamic 3-D MRI data. We apply our model using a data-driven technique based on a 2-D MRI image navigator. Unlike most previously reported work in the literature, our approach is able to capture both intra- and inter-cycle motion variability. In addition, the 2-D image navigator can be used to estimate how applicable the current motion model is, and hence report when more imaging data is required to update the model. We also use the motion model to decide on the best positioning for the image navigator. We validate our approach using MRI data acquired from 10 volunteers and demonstrate improvements of up to 40.5% over other reported motion modelling approaches, which corresponds to 61% of the overall respiratory motion present. Finally we demonstrate one potential application of our technique: MRI-based motion correction of real-time PET data for simultaneous PET-MRI acquisition.

Fast generation of 4D PET-MR data from real dynamic MR acquisitions.

We have implemented and evaluated a framework for simulating simultaneous dynamic PET-MR data using the anatomic and dynamic information from real MR acquisitions. PET radiotracer distribution is simulated by assigning typical FDG uptake values to segmented MR images with manually inserted additional virtual lesions. PET projection data and images are simulated using analytic forward projections (including attenuation and Poisson statistics) implemented within the image reconstruction package STIR. PET image reconstructions are also performed with STIR. The simulation is validated with numerical simulation based on Monte Carlo (GATE) which uses more accurate physical modelling, but has 150× slower computation time compared to the analytic method for ten respiratory positions and is 7000× slower when performing multiple realizations. Results are validated in terms of region of interest mean values and coefficients of variation for 65 million coincidences including scattered events. Although some discrepancy is observed, agreement between the two different simulation methods is good given the statistical noise in the data. In particular, the percentage difference of the mean values is 3.1% for tissue, 17% for the lungs and 18% for a small lesion. The utility of the procedure is demonstrated by simulating realistic PET-MR datasets from multiple volunteers with different breathing patterns. The usefulness of the toolkit will be shown for performance investigations of the reconstruction, motion correction and attenuation correction algorithms for dynamic PET-MR data.

Screening for Learning and Memory Mutations: A New Approach.

We describe a fully automated, live-in 24/7 test environment, with experimental protocols that measure the accuracy and precision with which mice match the ratio of their expected visit durations to the ratio of the incomes obtained from two hoppers, the progress of instrumental and classical conditioning (trials-to-acquisition), the accuracy and precision of interval timing, the effect of relative probability on the choice of a timed departure target, and the accuracy and precision of memory for the times of day at which food is available. The system is compact; it obviates the handling of the mice during testing; it requires negligible amounts of experimenter/technician time; and it delivers clear and extensive results from 3 protocols within a total of 7-9 days after the mice are placed in the test environment. Only a single 24-hour period is required for the completion of first protocol (the matching protocol), which is strong test of temporal and spatial estimation and memory mechanisms. Thus, the system permits the extensive screening of many mice in a short period of time and in limited space. The software is publicly available.

Registering preprocedure volumetric images with intraprocedure 3-D ultrasound using an ultrasound imaging model.

For many image-guided interventions there exists a need to compute the registration between preprocedure image(s) and the physical space of the intervention. Real-time intraprocedure imaging such as ultrasound (US) can be used to image the region of interest directly and provide valuable anatomical information for computing this registration. Unfortunately, real-time US images often have poor signal-to-noise ratio and suffer from imaging artefacts. Therefore, registration using US images can be challenging and significant preprocessing is often required to make the registrations robust. In this paper we present a novel technique for computing the image-to-physical registration for minimally invasive cardiac interventions using 3-D US. Our technique uses knowledge of the physics of the US imaging process to reduce the amount of preprocessing required on the 3-D US images. To account for the fact that clinical US images normally undergo significant image processing before being exported from the US machine our optimization scheme allows the parameters of the US imaging model to vary. We validated our technique by computing rigid registrations for 12 cardiac US/magnetic resonance imaging (MRI) datasets acquired from six volunteers and two patients. The technique had mean registration errors of 2.1-4.4 mm, and 75% capture ranges of 5-30 mm. We also demonstrate how the same approach can be used for respiratory motion correction: on 15 datasets acquired from five volunteers the registration errors due to respiratory motion were reduced by 45%-92%.

Respiratory motion correction for image-guided cardiac interventions using 3-D echocardiography.

In this paper, we investigate the use of 3-D echocardiography (echo) data for respiratory motion correction of roadmaps in image-guided cardiac interventions. This is made possible by tracking and calibrating the echo probe and registering it to the roadmap coordinate system. We compare two techniques. The first uses only echo-echo registration to predict a motion-correction transformation in roadmap coordinates. The second combines echo-echo registration with a model of the respiratory motion of the heart. Using experiments with cardiac MRI and 3-D echo data acquired from eight volunteers, we demonstrate that the second technique is more robust than the first, resulting in motion-correction transformations that were accurate to within 5mm in 60% of cases, compared to 42% for the echo-only technique, based on subjective visual assessments. Objective validation showed that the model-based technique had an accuracy of 3.3 + or - 1.1mm, compared to 4.1 + or - 2.2mm for the echo only technique. The greater errors of the echo-only technique were mostly found away from the area of echo coverage. The model-based technique was more robust away from this area, and also has significant benefits in terms of computational cost.

A subject-specific technique for respiratory motion correction in image-guided cardiac catheterisation procedures.

We describe a system for respiratory motion correction of MRI-derived roadmaps for use in X-ray guided cardiac catheterisation procedures. The technique uses a subject-specific affine motion model that is quickly constructed from a short pre-procedure MRI scan. We test a dynamic MRI sequence that acquires a small number of high resolution slices, rather than a single low resolution volume. Additionally, we use prior knowledge of the nature of cardiac respiratory motion by constraining the model to use only the dominant modes of motion. During the procedure the motion of the diaphragm is tracked in X-ray fluoroscopy images, allowing the roadmap to be updated using the motion model. X-ray image acquisition is cardiac gated. Validation is performed on four volunteer datasets and three patient datasets. The accuracy of the model in 3D was within 5mm in 97.6% of volunteer validations. For the patients, 2D accuracy was improved from 5 to 13mm before applying the model to 2-4mm afterwards. For the dynamic MRI sequence comparison, the highest errors were found when using the low resolution volume sequence with an unconstrained model.

Cultures, genes, and neurons in the development of song and singing in brown-headed cowbirds (Molothrus ater).

In brown-headed cowbirds, Molothrus ater, as in many songbird species, vocalizations are fundamental to reproduction. In our studies, experiments utilizing different social housing regimes and geographic comparisons have indicated the social learning of males' vocalizations and associated abilities to use vocalizations effectively during the breeding season. Here, we describe studies indicating roles of cultural and genetic background, and of social influences from females, on male vocal development. These influences can interact with neural regions, including song learning and song control nuclei, but also visual-processing nuclei, in the development of signaling. We argue that a developmental systems approach to the study of vocal behavior provides a structure to organize these different influences and how they may interact with one another over development. A systems approach requires that researchers study the social context in which signals and signalers develop - both the ontogenetic arena in which young animals learn their signals from older animals, and the functional arena in which young and older animals socially interact with one another.

The rat approximates an ideal detector of changes in rates of reward: implications for the law of effect.

Rats responded on 2 levers delivering brain stimulation reward on concurrent variable interval schedules. Following many successive sessions with unchanging relative rates of reward, subjects adjusted to an eventual change slowly and showed spontaneous reversions at the beginning of subsequent sessions. When changes in rates of reward occurred between and within every session, subjects adjusted to them about as rapidly as they could in principle do so, as shown by comparison to a Bayesian model of an ideal detector. This and other features of the adjustments to frequent changes imply that the behavioral effect of reinforcement depends on the subject's perception of incomes and changes in incomes rather than on the strengthening and weakening of behaviors in accord with their past effects or expected results. Models for the process by which perceived incomes determine stay durations and for the process that detects changes in rates are developed.

Cultural transmission of vocal traditions in cowbirds (Molothrus ater) influences courtship patterns and mate preferences.

In this study, the authors tested the cultural transmission of vocal traditions in cowbirds (Molothrus ater). Young cowbirds from a South Dakota (SD) population were housed over winter with adults of the SD population or with adults from an Indiana (IN) population. Song differences between the original SD and IN adult models were acquired by South Dakota culture (SDC) and Indiana culture (INC) males, respectively, and were transmitted to a 2nd cultural generation of birds. During playback tests of SDC and INC songs, SD females gave more copulatory responses to SDC songs. Finally, males with SD-like songs courted SDC females preferentially in breeding season tests, whereas males with IN-like songs courted INC females preferentially. These results indicate that the transmission of vocal traditions plays a fundamental role in the courtship patterns and mating decisions of cowbirds.

Dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum: a lesion often misdiagnosed as glioma: report of 10 cases.

The authors report a series of 10 low-grade neoplasms arising in the midline anteriorly in the region of the septum pellucidum with many of the histologic features of dysembryoplastic neuroepithelial tumor (DNT). The patients (five female, five male) ranged in age from 6 to 35 years (mean age, 21.5 years). The most common presenting symptoms were headache, nausea and vomiting, and visual disturbances. Radiographically, the tumors extended into the lateral ventricles from the septal region and obstructed the foramen of Monro. Varying degrees of hydrocephalus were present. The lesions were lobular, well-delineated, hypointense to brain on T1-weighted magnetic resonance imaging, and hyperintense on T2-weighted images. They were uniformly nonenhancing or showed only minimal peripheral enhancement. The tumors, in aggregate, had the histologic features of DNT. These included a mucin-rich background, oligodendrocyte-like cells, "floating neurons," and a "specific glioneuronal element." Seven patients underwent gross total resection and two underwent subtotal resection. No patients received adjuvant chemotherapy or radiotherapy. On follow-up (n = 6; median, 14 months), all tumors had either not recurred or were radiologically stable. On the basis of both neuroimaging and histopathology, DNT-like lesions should be considered in the differential diagnosis of midline intraventricular tumors in children and young adults. Distinction from more aggressive neoplasms is essential because these tumors appear to behave in a benign fashion.

Functional expression of L-, N-, P/Q-, and R-type calcium channels in the human NT2-N cell line.

The biophysical and pharmacological properties of voltage-gated calcium channel currents in the human teratocarcinoma cell line NT2-N were studied using the whole cell patch-clamp technique. When held at -80 mV, barium currents (I(Ba)s) were evoked by voltage commands to above -35 mV that peaked at +5 mV. When holding potentials were reduced to -20 mV or 5 mM barium was substituted for 5 mM calcium, there was a reduction in peak currents and a right shift in the current-voltage curve. A steady-state inactivation curve for I(Ba) was fit with a Boltzmann curve (V(1/2) = -43.3 mV; slope = -17.7 mV). Maximal current amplitude increased from 1-wk (232 pA) to 9-wk (1025 pA) postdifferentiation. Whole cell I(Ba)s were partially blocked by specific channel blockers to a similar extent in 1- to 3-wk and 7- to 9-wk postdifferentiation NT2-N cells: 10 microM nifedipine (19 vs. 25%), 10 microM conotoxin GVIA (27 vs. 25%), 10 microM conotoxin MVIIC (15 vs. 16%), and 1.75 microM SNX-482 (31 vs. 33%). Currents were completely blocked by 300 microM cadmium. In the presence of nifedipine, GVIA, and MVIIC, approximately 35% of current remained, which was reduced further by SNX-482 (7-14% of current remained), consistent with functional expression of L-, N-, and P/Q-calcium channel types and one or more R-type channel. The presence of multiple calcium currents in this human neuronal-type cell line provides a potentially useful model for study of the regulation, expression and cellular function of human derived calcium channel currents; in particular the R-type current(s).

Locking acrylic resin dental stent for image-guided surgery.

This article presents a procedure for fabricating a locking acrylic resin dental stent for use in image-guided base-of-skull surgery and neurosurgery. The stent offers advantages over conventional bone screw-anchored systems to surgeons and patients. In view of the increasing use of image guidance in base-of-skull surgery and neurosurgery, prosthodontists will meet a growing demand for this type of device in the future.

Design and evaluation of a system for microscope-assisted guided interventions (MAGI).

The problem of providing surgical navigation using image overlays on the operative scene can be split into four main tasks--calibration of the optical system; registration of preoperative images to the patient; system and patient tracking, and display using a suitable visualization scheme. To achieve a convincing result in the magnified microscope view a very high alignment accuracy is required. We have simulated an entire image overlay system to establish the most significant sources of error and improved each of the stages involved. The microscope calibration process has been automated. We have introduced bone-implanted markers for registration and incorporated a locking acrylic dental stent (LADS) for patient tracking. The LADS can also provide a less-invasive registration device with mean target error of 0.7 mm in volunteer experiments. These improvements have significantly increased the alignment accuracy of our overlays. Phantom accuracy is 0.3-0.5 mm and clinical overlay errors were 0.5-1.0 mm on the bone fiducials and 0.5-4 mm on target structures. We have improved the graphical representation of the stereo overlays. The resulting system provides three-dimensional surgical navigation for microscope-assisted guided interventions (MAGI).

Stereo augmented reality in the surgical microscope.

We present an augmented reality system that allows surgeons to view features from preoperative radiological images accurately overlaid in stereo in the optical path of a surgical microscope. The purpose of the system is to show the surgeon structures beneath the viewed surface in the correct 3-D position. The technical challenges are registration, tracking, calibration and visualisation. For patient registration, or alignment to preoperative images, we use bone-implanted markers and a dental splint is used for patient tracking. Both microscope and patient are tracked by an optical localiser. Calibration uses an accurately manufactured object with high contrast circular markers which are identified automatically. All ten camera parameters are modelled as a bivariate polynomial function of zoom and focus. The overall system has a theoretical overlay accuracy of better than 1 mm. Implementations of the system have been tested on seven patients. Recent measurements in the operating room conformed to our accuracy predictions. For visualisation the system has been implemented on a graphics workstation to enable high frame rates with a variety of rendering schemes. Several issues of 3-D depth perception remain unsolved, but early results suggest that perception of structures in the correct 3-D position beneath the viewed surface is possible.

kappa- and mu-Opioid inhibition of N-type calcium currents is attenuated by 4beta-phorbol 12-myristate 13-acetate and protein kinase C in rat dorsal root ganglion neurons.

In rat dorsal root ganglion neurons, activation of kappa- and mu-opioid receptors decreases N-type calcium current, whereas a constitutively active form of protein kinase C (PKC; i.e., PKM, a PKC catalytic subunit fragment) increases N-type calcium current. PKC also attenuates inhibition of calcium current by several G protein-linked neurotransmitter systems. We examined the effects of activation of endogenous PKC by 4beta-phorbol 12-myristate 13-acetate (PMA) and dialysis of cells with PKM and a pseudosubstrate inhibitor PKC(19-31) (PKC-I) on kappa- and mu-opioid-mediated inhibition of calcium current, calcium current amplitude, and rundown. PMA modestly increased peak calcium current and substantially reduced calcium current "rundown," effects blocked by PKC-I. In contrast, PKC-I decreased calcium current and increased current rundown. PMA attenuated morphine-, dynorphin A-, and U50, 488- but not pentobarbitol-related inhibition of calcium current. Similar effects were seen with intracellular dialysis of PKM. Intracellular PKC-I did not block opioid inhibition of calcium current but did reverse PMA and PKM effects on opioid receptor coupling to calcium channels. Because neither PMA nor PKM changed the proportion of omega-CgTX-inhibited current, their effects were not due to a decrease in the proportion of N-type current. After omega-CgTX treatment, there were no differences in the dynorphin A effects on control and PMA- or PKM-treated neurons, suggesting that PKC primarily affected coupling to N-type calcium channels. These data suggest that in acutely dissociated rat dorsal root ganglion neurons, endogenous PKC is required for maintenance of calcium current, may play a role in regulation of neuronal calcium channels, and could be involved in tolerance and/or cross-talk inhibition of opioid responsiveness.