Comparison of Methods and Co-Registration Maps of EEG and fMRI in Occipital Lobe Epilepsy

Clinically childhood occipital lobe epilepsy (OLE) manifests itself with distinct syndromes. The traditional EEG recordings have not been able to overcome the difficulty in correlating the ictal clinical symptoms to the onset in particular areas of the occipital lobes. To understand these syndromes it is important to map with more precision the epileptogenic cortical regions in OLE. Experimentally, we studied three idiopathic childhood OLE patients with EEG source analysis and with the simultaneous acquisition of EEG and fMRI, to map the BOLD effect associated with EEG spikes. The spatial overlap between the EEG and BOLD results was not very good, but the fMRI suggested localizations more consistent with the ictal clinical manifestations of each type of epileptic syndrome. Since our first results show that by associating the BOLD effect with interictal spikes the epileptogenic areas are mapped to localizations different from those calculated from EEG sources and that by using different EEG/fMRI processing methods our results differ to some extent, it is very important to compare the different methods of processing the localization of activation and develop a good methodology for obtaining co-registration maps of high resolution EEG with BOLD localizations.

EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration

the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated.

Co-registration of magnetoencephalography with magnetic resonance imaging using bite-bar-based fiducials and surface-matching

Objective: To introduce a new technique for co-registration of Magnetoencephalography (MEG) with magnetic resonance imaging (MRI). We compare the accuracy of a new bite-bar with fixed fiducials to a previous technique whereby fiducial coils were attached proximal to landmarks on the skull. Methods: A bite-bar with fixed fiducial coils is used to determine the position of the head in the MEG co-ordinate system. Co-registration is performed by a surface-matching technique. The advantage of fixing the coils is that the co-ordinate system is not based upon arbitrary and operator dependent fiducial points that are attached to landmarks (e.g. nasion and the preauricular points), but rather on those that are permanently fixed in relation to the skull. Results: As a consequence of minimizing coil movement during digitization, errors in localization of the coils are significantly reduced, as shown by a randomization test. Displacement of the bite-bar caused by removal and repositioning between MEG recordings is minimal (∼0.5 mm), and dipole localization accuracy of a somatosensory mapping paradigm shows a repeatability of ∼5 mm. The overall accuracy of the new procedure is greatly improved compared to the previous technique. Conclusions: The test-retest reliability and accuracy of target localization with the new design is superior to techniques that incorporate anatomical-based fiducial points or coils placed on the circumference of the head. © 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Magnetoencephalography:technical improvements in image co-registration and studies of visual cortical oscillations

The work presented in this thesis is divided into two distinct sections. In the first, the functional neuroimaging technique of Magnetoencephalography (MEG) is described and a new technique is introduced for accurate combination of MEG and MRI co-ordinate systems. In the second part of this thesis, MEG and the analysis technique of SAM are used to investigate responses of the visual system in the context of functional specialisation within the visual cortex. In chapter one, the sources of MEG signals are described, followed by a brief description of the necessary instrumentation for accurate MEG recordings. This chapter is concluded by introducing the forward and inverse problems of MEG, techniques to solve the inverse problem, and a comparison of MEG with other neuroimaging techniques. Chapter two provides an important contribution to the field of research with MEG. Firstly, it is described how MEG and MRI co-ordinate systems are combined for localisation and visualisation of activated brain regions. A previously used co-registration methods is then described, and a new technique is introduced. In a series of experiments, it is demonstrated that using fixed fiducial points provides a considerable improvement in the accuracy and reliability of co-registration. Chapter three introduces the visual system starting from the retina and ending with the higher visual rates. The functions of the magnocellular and the parvocellular pathways are described and it is shown how the parallel visual pathways remain segregated throughout the visual system. The structural and functional organisation of the visual cortex is then described. Chapter four presents strong evidence in favour of the link between conscious experience and synchronised brain activity. The spatiotemporal responses of the visual cortex are measured in response to specific gratings. It is shown that stimuli that induce visual discomfort and visual illusions share their physical properties with those that induce highly synchronised gamma frequency oscillations in the primary visual cortex. Finally chapter five is concerned with localization of colour in the visual cortex. In this first ever use of Synthetic Aperture Magnetometry to investigate colour processing in the visual cortex, it is shown that in response to isoluminant chromatic gratings, the highest magnitude of cortical activity arise from area V2.

Otimização do co-registo metabolismo-morfologia em estudos de PET/CT com 18F-DG de nódulos pulmonares: comparação de dois protocolos - 4D vs CT lento

Mestrado em Medicina Nuclear - Área de especialização: Tomografia por Emissão de Positrões.

Improved detection of incipient vascular changes by a biotechnological platform combining post mortem MRI in situ with neuropathology

The histopathological counterpart of white matter hyperintensities is a matter of debate. Methodological and ethical limitations have prevented this question to be elucidated. We want to introduce a protocol applying state-of-the-art methods in order to solve fundamental questions regarding the neuroimaging-neuropathological uncertainties comprising the most common white matter hyperintensities [WMHs] seen in aging. By this protocol, the correlation between signal features in in situ, post mortem MRI-derived methods, including DTI and MTR and quantitative and qualitative histopathology can be investigated. We are mainly interested in determining the precise neuroanatomical substrate of incipient WMHs. A major issue in this protocol is the exact co-registration of small lesion in a tridimensional coordinate system that compensates tissue deformations after histological processing. The protocol is based on four principles: post mortem MRI in situ performed in a short post mortem interval, minimal brain deformation during processing, thick serial histological sections and computer-assisted 3D reconstruction of the histological sections. This protocol will greatly facilitate a systematic study of the location, pathogenesis, clinical impact, prognosis and prevention of WMHs. (C) 2009 Elsevier B.V. All rights reserved.

Avaliação da distribuição de dose no CTV-PTV através de imagem guiada em doentes com carcinoma da próstata

Mestrado em Radioterapia.

Quantification of the TMS-EEG response in epilepsy

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Discrimination of cortical laminae using MEG.

Typically MEG source reconstruction is used to estimate the distribution of current flow on a single anatomically derived cortical surface model. In this study we use two such models representing superficial and deep cortical laminae. We establish how well we can discriminate between these two different cortical layer models based on the same MEG data in the presence of different levels of co-registration noise, Signal-to-Noise Ratio (SNR) and cortical patch size. We demonstrate that it is possible to make a distinction between superficial and deep cortical laminae for levels of co-registration noise of less than 2mm translation and 2° rotation at SNR>11dB. We also show that an incorrect estimate of cortical patch size will tend to bias layer estimates. We then use a 3D printed head-cast (Troebinger et al., 2014) to achieve comparable levels of co-registration noise, in an auditory evoked response paradigm, and show that it is possible to discriminate between these cortical layer models in real data.

Temporo-Parietal Junction encodes the Embodied Self: Neuro-Robotics, fMRI, and Lesion mapping.

Introduction: Neuroimaging of the self focused on high-level mechanisms such as language, memory or imagery of the self. Recent evidence suggests that low-level mechanisms of multisensory and sensorimotor integration may play a fundamental role in encoding self-location and the first-person perspective (Blanke and Metzinger, 2009). Neurological patients with out-of body experiences (OBE) suffer from abnormal self-location and the first-person perspective due to a damage in the temporo-parietal junction (Blanke et al., 2004). Although self-location and the first-person perspective can be studied experimentally (Lenggenhager et al., 2009), the neural underpinnings of self-location have yet to be investigated. To investigate the brain network involved in self-location and first-person perspective we used visuo-tactile multisensory conflict, magnetic resonance (MR)-compatible robotics, and fMRI in study 1, and lesion analysis in a sample of 9 patients with OBE due to focal brain damage in study 2. Methods: Twenty-two participants saw a video showing either a person's back or an empty room being stroked (visual stimuli) while the MR-compatible robotic device stroked their back (tactile stimulation). Direction and speed of the seen stroking could either correspond (synchronous) or not (asynchronous) to those of the seen stroking. Each run comprised the four conditions according to a 2x2 factorial design with Object (Body, No-Body) and Synchrony (Synchronous, Asynchronous) as main factors. Self-location was estimated using the mental ball dropping (MBD; Lenggenhager et al., 2009). After the fMRI session participants completed a 6-item adapted from the original questionnaire created by Botvinick and Cohen (1998) and based on questions and data obtained by Lenggenhager et al. (2007, 2009). They were also asked to complete a questionnaire to disclose the perspective they adopted during the illusion. Response times (RTs) for the MBD and fMRI data were analyzed with a 3-way mixed model ANOVA with the in-between factor Perspective (up, down) and the two with-in factors Object (body, no-body) and Stroking (synchronous, asynchronous). Quantitative lesion analysis was performed using MRIcron (Rorden et al., 2007). We compared the distributions of brain lesions confirmed by multimodality imaging (Knowlton, 2004) in patients with OBE with those showing complex visual hallucinations involving people or faces, but without any disturbance of self-location and first person perspective. Nine patients with OBE were investigated. The control group comprised 8 patients. Structural imaging data were available for normalization and co-registration in all the patients. Normalization of each patient's lesion into the common MNI (Montreal Neurological Institute) reference space permitted simple, voxel-wise, algebraic comparisons to be made. Results: Even if in the scanner all participants were lying on their back and were facing upwards, analysis of perspective showed that half of the participants had the impression to be looking down at the virtual human body below them, despite any cues about their body position (Down-group). The other participants had the impression to be looking up at the virtual body above them (Up-group). Analysis of Q3 ("How strong was the feeling that the body you saw was you?") indicated stronger self-identification with the virtual body during the synchronous stroking. RTs in the MBD task confirmed these subjective data (significant 3-way interaction between perspective, object and stroking). fMRI results showed eight cortical regions where the BOLD signal was significantly different during at least one of the conditions resulting from the combination of Object and Stroking, relative to baseline: right and left temporo-parietal junction, right EBA, left middle occipito-temporal gyrus, left postcentral gyrus, right medial parietal lobe, bilateral medial occipital lobe (Fig 1). The activation patterns in right and left temporo-parietal junction and right EBA reflected changes in self-location and perspective as revealed by statistical analysis that was performed on the percentage of BOLD change with respect to the baseline. Statistical lesion overlap comparison (using nonparametric voxel based lesion symptom mapping) with respect to the control group revealed the right temporo-parietal junction, centered at the angular gyrus (Talairach coordinates x = 54, y =-52, z = 26; p>0.05, FDR corrected). Conclusions: The present questionnaire and behavioural results show that - despite the noisy and constraining MR environment) our participants had predictable changes in self-location, self-identification, and first-person perspective when robotic tactile stroking was applied synchronously with the robotic visual stroking. fMRI data in healthy participants and lesion data in patients with abnormal self-location and first-person perspective jointly revealed that the temporo-parietal cortex especially in the right hemisphere encodes these conscious experiences. We argue that temporo-parietal activity reflects the experience of the conscious "I" as embodied and localized within bodily space.

High precision anatomy for MEG.

Precise MEG estimates of neuronal current flow are undermined by uncertain knowledge of the head location with respect to the MEG sensors. This is either due to head movements within the scanning session or systematic errors in co-registration to anatomy. Here we show how such errors can be minimized using subject-specific head-casts produced using 3D printing technology. The casts fit the scalp of the subject internally and the inside of the MEG dewar externally, reducing within session and between session head movements. Systematic errors in matching to MRI coordinate system are also reduced through the use of MRI-visible fiducial markers placed on the same cast. Bootstrap estimates of absolute co-registration error were of the order of 1mm. Estimates of relative co-registration error were <1.5mm between sessions. We corroborated these scalp based estimates by looking at the MEG data recorded over a 6month period. We found that the between session sensor variability of the subject's evoked response was of the order of the within session noise, showing no appreciable noise due to between-session movement. Simulations suggest that the between-session sensor level amplitude SNR improved by a factor of 5 over conventional strategies. We show that at this level of coregistration accuracy there is strong evidence for anatomical models based on the individual rather than canonical anatomy; but that this advantage disappears for errors of greater than 5mm. This work paves the way for source reconstruction methods which can exploit very high SNR signals and accurate anatomical models; and also significantly increases the sensitivity of longitudinal studies with MEG.

PS-GANS: A Patient-Specific, Gravity Assisted Navigation System for Acetabular Cup Placement

In this paper we propose a new system that allows reliable acetabular cup placement when the THA is operated in lateral approach. Conceptually it combines the accuracy of computer-generated patient-specific morphology information with an easy-to-use mechanical guide, which effectively uses natural gravity as the angular reference. The former is achieved by using a statistical shape model-based 2D-3D reconstruction technique that can generate a scaled, patient-specific 3D shape model of the pelvis from a single conventional anteroposterior (AP) pelvic X-ray radiograph. The reconstructed 3D shape model facilitates a reliable and accurate co-registration of the mechanical guide with the patient’s anatomy in the operating theater. We validated the accuracy of our system by conducting experiments on placing seven cups to four pelvises with different morphologies. Taking the measurements from an image-free navigation system as the ground truth, our system showed an average accuracy of 2.1 ±0.7 o for inclination and an average accuracy of 1.2 ±1.4 o for anteversion.

Registry for the Evaluation of the Prognostik value of a novel integrated imaging approach combining Single Photon Emission Computed Tomography with coronary calcification imaging (REPROSPECT)

AIMS: Although an added diagnostic and prognostic value of the global coronary artery calcification (CAC) score as an adjunct to single-photon emission computed tomography (SPECT)-myocardial perfusion image (MPI) has been repeatedly documented, none of the previous studies took advantage of the anatomic information provided by the unenhanced cardiac CT. Therefore, no co-registration has so far been used to match a myocardial perfusion defect with calcifications in the subtending coronary artery. To evaluate the prognostic value of integrating SPECT-MPI with CAC images were obtained from non-enhanced cardiac computed tomography (CT) for attenuation correction to predict major adverse cardiac events (MACE). METHODS AND RESULTS: Follow-up was obtained in 462 patients undergoing a 1-day stress/rest (99m)Tc-teterofosmin SPECT and non-enhanced cardiac CT for attenuation correction. Survival free of MACE was determined using the Kaplan-Meier method. After integrating MPI and CT findings, patients were divided into three groups (i) MPI defect matched by calcification (CAC ≥ 1) in the subtending coronary artery (ii) unmatched MPI and CT finding (iii) normal finding by MPI and CT. At a mean follow-up of 34.5 ± 13 months, a MACE was observed in 80 patients (33 death, 6 non-fatal myocardial infarction, 9 hospitalizations due to unstable angina, and 32 revascularizations). Survival analysis revealed the most unfavourable outcome (P < 0.001 log-rank test) for patients with a matched finding. CONCLUSION: In the present study, a novel approach using a combined integration of cardiac SPECT-CAC imaging allows for refined risk stratification, as a matched defect emerged as an independent predictor of MACE.

The role of 3D fusion imaging in sentinel lymphadenectomy for vulvar cancer

OBJECTIVES: To evaluate the feasibility of fusion imaging compound tomography (FICT) of CT/MRI and single photon emission tomography (SPECT) versus planar scintigraphy only (plSc) in pre-surgical staging for vulvar cancer. MATERIALS AND METHODS: Analysis of consecutive patients with vulvar cancer who preoperatively underwent sentinel scintigraphy (planar and 3D-SPECT imaging) and CT or MRI. Body markers were used for exact anatomical co-registration and fusion datasets were reconstructed using SPECT and CT/MRI. The number and localisation of all intraoperatively identified and resected sentinel lymph nodes (SLN) were compared between planar and 3D fusion imaging. RESULTS: Twenty six SLN were localized on planar scintigraphy. Twelve additional SLN were identified after SPECT and CT/MRI reconstruction, all of them were confirmed intraoperatively. In seven cases where single foci were identified at plSc, fusion imaging revealed grouped individual nodes and five additional localisations were discovered at fusion imaging. In seven patients both methods identified SLN contra lateral to the primary tumor site, but only fusion imaging allowed to localise iliac SLN in four patients. All SLN predicted on fusion imaging could be localised and resected during surgery. CONCLUSIONS: Fusion imaging using SPECT and CT/MRI can detect SLN in vulvar cancer more precisely than planar imaging regarding number and anatomical localisation. FICT revealed additional information in seven out of ten cases (70%).