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The main purpose of multimodality imaging is to provide an advanced diagnostic tool by combining measurements of anatomy and physiology obtained with different techniques – in particular PET-TC and PET/MRI. Multimodality imaging can refer to two main fronts each characterized by the space-time context of data acquisition. Either such morphofunctional, multimodal images are generated by fusing images acquired with each technique separately and at different times or they may arise from truly contextual or simultaneous acquisitions. In this latter case, we are speaking of a hybrid system. There are many potential advantages of hybrid imaging, since ideally both anatomical and functional information can be obtained at the same time without any time delays between modalities and without any need for coregistration of the image information. Beyond this attractive prospect, there are some pivotal synergistic effects that come with the integration of multiple modalities, mainly relating to correcting PET data to yield truly quantitative information while maximizing the signal-to-noise ratio. In this chapter we shall briefly recall some basic physics concepts of each single and combined imaging technique: PET, CT, and MRI.

Obstructive sleep apnea (OSA) is accompanied by neurocognitive impairment, likely mediated by injury to various brain regions. We evaluated brain morphological changes in patients with OSA and their relationship to neuropsychological and oximetric data. Sixteen patients affected by moderate-severe OSA (age: 55.8±6.7 years, 13 males) and fourteen control subjects (age: 57.6±5.1 years, 9 males) underwent 3.0 Tesla brain magnetic resonance imaging (MRI) and neuropsychological testing evaluating short and long-term memory, executive functions, language, attention, praxia and non-verbal learning. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry (VBM) were performed. Patients and controls differed significantly in Rey Auditory- Verbal Learning test (immediate and delayed recall), Stroop test and Digit span backward scores. Volumes of cortical gray matter (GM), right hippocampus, right and left caudate were smaller in patients compared to controls, with also brain parenchymal fraction (a normalized measure of cerebral atrophy) approaching statistical significance. Differences remained significant after controlling for comorbidities (hypertension, diabetes, smoking, hypercholesterolemia). VBM analysis showed regions of decreased GM volume in right and left hippocampus and within more lateral temporal areas in patients with OSA. Our findings indicate that the significant cognitive impairment seen in patients with moderate-severe OSA is associated with brain tissue damage in regions involved in several cognitive tasks. We conclude that OSA can increase brain susceptibility to the effects of aging and other clinical and pathological occurrences.

The Directive 2013/35/EU establishes standards for workers exposed to static and time varying magnetic fields. These limits are based on ICNIRP guidelines expressed in terms of the electric field induced in the body. The complexity of this measurement led to theoretical models being developed. In this study, the experimental evaluation included varying magnetic field exposures for two classes of MRI workers. The measurements are conducted on four different MRI Systems including one 0.35 T, two 1.5 T, and one 3.0 T. Pocket magnetic dosimeters were used and it was carried out during routine conditions, emergency conditions, and cold-head maintenance/substitution. The acquired data has been processed and the corresponding dB/dt curves have been computed as the first time derivative of the dataset. The weighted peak approach was also implemented for the compliance assessment with regulatory limits. The dB/dt peak values have been compared with the reference level (RL) proposed by ICNIRP. The results show that the RL always exceeds during measurements on the 3.0 T scanner and sometimes on 1.5 T. In light of the foregoing, the diffusion of ultra-high field MRI scanners involves the introduction of behavioral rules that could be more useful than a numerical action level.

The evaluation of the performances of brain-computer interface (BCI) systems could be difficult as a standard procedure does not exist. In fact, every research team creates its own experimental protocol (different input signals, different trial structure, different output devices, etc.) and this makes systems comparison difficult. Moreover, the great question is whether these experiments can be extrapolated to real world applications or not. To overcome some intrinsic limitations of the most used criteria a new efficiency indicator will be described and used. Its main advantages are that it can predict with a high accuracy the performances of a whole system, a fact that can be used to successfully improve its behavior. Finally, simulations were performed to illustrate that the best system is built by tuning the transducer (TR) and the control interface (CI), which are the two main components of a BCI system, so that the best TR and the best CI do not exist but just the best combination of them.

Overheating during implant site preparation negatively affects the osseointegration process as well the final outcome of implant rehabilitations. Piezoelectric techniques seem to provide to a gentle implant preparation although few scientific reports have investigated the heat generation and its underlying factors. To investigate, through a proper methodological approach, the main factors influencing temperature rise during piezoelectric implant site preparation. Different piezoelectric tips (IM1s, IM2, P2-3, IM3, Mectron Medical Technology, Carasco, Italy) have been tested. The experimental set-up consisted in a mechanical positioning device equipped with a load cell and a fluoroptic thermometer. The first tip of the sequence (IM1s) generated the highest temperature increasing (ΔT). The diamond tips (IM1s and P2-3) determined higher ΔT values than the smooth tips (IM2 and IM3). Further tests with IM1s suggested that the temperature elevation during the first thirty seconds may be predictive of the maximal temperature as well as of the overall thermal impact. Working load, working movements management and bone features resulted to be the main factors influencing temperature rise during piezoelectric implant site preparation. Irrigant temperature and clogging effect may also synergically contribute to the heat generation.

The purpose of this study was to investigate short-time metabolic variations related to continuous epileptic activity elicited by fixation-off sensitivity (FOS). Time-resolved magnetic resonance spectroscopy was performed on a patient on whom previous clinical findings clearly indicated presence of FOS. The epileptic focus was localized with a simultaneous electroencephalographic and functional magnetic resonance imaging study. The results showed a linear increase of the sum of glutamate and glutamine with time of paroxysmal activity in epileptic focus and much greater concentration of choline-containing compounds in focus than in the contralateral side.

A chemical shift imaging (CSI) study was performed to directly assess relative concentrations of N-acetylaspartate (NAA), Cho and Cr metabolites in normal- and abnormal-appearing brain tissue of asymptomatic and symptomatic members of a single family with a neuropathologic, genetic and electrophysiological confirmed diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The aim of the investigation was to evaluate clinical findings and metabolite abnormalities as early appearance of axonal injury in this syndrome. The main findings related statistically significant decreases in the mean metabolite ratios for NAA/Cr, NAA/Cho and Cho/Cr in the anterior parts in comparison with the posterior parts of the centrum semiovale in symptomatic and asymptomatic patients. The effect was considerably greater in the symptomatic patients, indicating a strong correlation between CSI and pathology results. No differences were found between the two areas in the control group. Although lactate signals were hardly detectable in individual spectra, there was a trend toward increased Lac/Cr values in the anterior parts with respect to the posterior parts in the patient group, with the effect particularly evident in the asymptomatic subjects with the gene mutation. (c) 2006 Elsevier Inc. All rights reserved.

Tourette syndrome (TS) is hypothesised to be caused by an abnormal organization of movement control. The aim of this study was to use functional magnetic resonance imaging to study motor cortex activation in a TS patient. Usual and unusual self-paced voluntary movements were performed. The TS patient displayed supplementary motor area (SMA) activation during both tasks. This activation reflects a continuous use of the SMA to perform the voluntary motor movements required in both tasks. Moreover, the absence of tics during the execution of these voluntary motor tasks suggests that tic activity may be suppressed by additional mental effort.

Noninvasive functional studies on human spinal cord by means of magnetic resonance imaging (MRI) are gaining attention because of the promising applications in the study of healthy and injured central nervous system. The findings obtained are generally consistent with the anatomic knowledge based on invasive methods, but the origin and specificity of functional contrast is still debated. In this paper, a review of current knowledge and major issues about functional MRI (fMRI) in the human spinal cord is presented, with emphasis on the main methodological and technical problems and on forthcoming applications as clinical tool.

A standard EEG equipment was modified in order to work properly during ultra-fast MRI acquisitions. Changes include: amagnetic electrode cap, optical fiber link, shielding box for EEG amplifier, twisted low metal mass cable. The effects of the RF pulse and time varying magnetic fields were minimized by using a correct head cap wires locked environment montage and then removed with a simple subtraction algorithm during EEG/fMRI acquisition. Ballistocardiogram artifact was also minimized at suitable levels by using a comfortable head position and immobilization.

In the present work, an arteriovenous malformation was taken as a pathological model for studying task-related flow decreases during a motor task. Combined Blood Oxygen Level Dependent (BOLD)-perfusion experiments were applied in order to evaluate the relative sensitivity of these techniques to task-related reductions in cerebral blood flow (CBF). Results shows that, by matching the sensitivity of the methods (which exhibit a different contrast-to-noise ratio) in the primary motor cortex, the spatial extent of the regions of decreased perfusion signal is larger than those of the BOLD signal reduction. The above finding suggests that perfusion imaging, that already represents a gold standard method in the detection of vascular phenomena, may estimate task-related flow decreases in a functional time-series better than BOLD.

In this article, a review is made of the current knowledge concerning the physiology and metabolism of neuronal activity, as provided by the application of NMR approaches in vivo. The evidence furnished by other functional spectroscopic and imaging techniques, such as PET and optical methods, are also discussed. In spite of considerable amounts of studies presented in the literature, several controversies concerning the mechanisms underlying brain function still remain, mainly due to the difficult assessment of the single vascular and metabolic dynamics which generally influence the functional signals. In this framework, methodological and technical improvements are required to provide new and reliable experimental elements, which can support or eventually modify the current models of activation.

The metabolic events of neuronal energetics during functional activity are still partially unexplained. In particular, lactate (and not glucose) was recently proposed as the main substrate for neurons during activity [Proc Natl Acad Sci USA 91 (1994) 10625] . By means of proton magnetic resonance spectroscopy, lactate was reported to increase during the first minutes of prolonged stimulation Prichard et al 1991 , Sappey-Marinier et al 1992 , Frahm et al 1996 , but the studies reported thus far suffered from low temporal resolution. In the present study we used a time-resolved proton magnetic resonance spectroscopy strategy in order to analyse the evolution of lactate during the early seconds following a brief visual stimulation (event-related design). A significant decrease in lactate concentration was observed 5 s after the stimulation, while a recovering of the baseline was observed at 12 s.

The fast developing and newly emerging nuclear magnetic resonance methods for functional brain imaging are discussed. The main features of blood-oxygen-level-dependent (BOLD) imaging and perfusion imaging are exposed together with their limitations. The combination of localized spectroscopy with magnetic resonance imaging (MRI) and neuronal activation provide the crucial metabolic information, which is complementary to the physiological data given by BOLD and perfusion imaging. Finally, the diffusion tensor imaging and the nonlinear MRI, with the perspective of getting information about the “architecture” of the axonal connections and of the macrostructures are discussed.

In questo lavoro vengono affrontati alcuni argomenti che sono al centro della più recente indagine scientifica nel campo delle neuroscienze, in relazione alle metodologie che utilizzano la risonanza magnetica nucleare nello studio della funzionalita cerebrale. Soprattutto grazie alle sue caratteristiche di non invasività, la risonanza magnetica funzionale non soltanto si presenta come un formidabile strumento di ricerca finalizzato alla comprensione delle relazioni che intercorrono tra la struttura cerebrale, la funzionalità cerebrale e le patologie neurologiche, ma si prospetta anche come un'importante tecnica diagnostica di routine clinica. Tuttavia le problematiche legate a tale metodologia sono molteplici, e riguardano da una parte l'interpretazione stessa del segnale rivelato in condizioni di attivazione neuronale, dall'altra la definizione della risoluzione spazio-temporale, della specificità spaziale e della significatività statistica delle mappe di attivazione ottenute.

Parkinson's disease is a neurological disorder associated with the disfunction of dopaminergic pathways of the basal ganglia, mainly resulting in a progressive alteration in the execution of voluntary movements. We present a functional magnetic resonance imaging (fMRI) study on cortical activations during simple motor task performance, in six early–stage hemiparkinsonian patients and seven healthy volunteers. We acquired data in three sessions, during which subjects performed the task with right or left hand, or bimanually. We observed consistent bilateral activations in cingulate cortex and dorsolateral prefrontal cortex of Parkinsonian subjects during the execution of the task with the affected hand. In addition, patients showed both larger and stronger activations in motor cortex of the affected hemisphere with respect to the healthy hemisphere. Compared with the control group, patients showed a hyperactivation of the dorsolateral prefrontal cortex of the affected hemisphere. We concluded that a presymptomatic reorganization of the motor system is likely to occur in Parkinson's disease at earlier stages than previously hypothesized. Moreover, our results support fMRI as a sensitive technique for revealing the initial involvement of motor cortex areas at the debut of this degenerative disorder.

l-2-Hydroxyglutaric aciduria (l-2-HGA) is a neurometabolic disease characterized by the presence of elevated levels of 2-hydroxyglutaric acid in the plasma, cerebrospinal fluid and urine. Clinical features in this inherited condition consist of mental deterioration, ataxia and motor deficits with pyramidal and extrapyramidal symptoms and signs. l-2-HGA is caused by mutations in the l-2-HGDH gene which most probably encodes for a l-2-hydroxyglutarate dehydrogenase, a putative mitochondrial protein converting l-2-hydroxyglutarate to alphaketoglutarate. Here, we report a pathogenic nonsense mutation in the l-2-HGDH gene found for the first time in an Italian patient affected by l-2-HGA, reinforcing the previously described phenotype of this rare metabolic disease and confirming the data indicating that mutations in the l-2-HGDH gene cause l-2-HGA. © 2010 Springer-Verlag.

Objective: Aim of the study was to record BOLD-fMRI interleaved with evoked potentials for singleepochs of visual stimulation and to investigate the possible relationship between these two measures. Methods: Sparse recording of fMRI and EEG allowed us to measure BOLD responses and evoked potentials on an epoch-by-epoch basis. To obtain robust estimates of evoked potentials, we used blocks of contrastreversing visual stimuli eliciting steady-state visual evoked potentials (SSVEPs). For each block we acquired one volume of fMRI data and we then tested for co-variations between SSVEPs and fMRI signals. Our analyses tested for frequency-specific co-variation between the two measurements that could not be explained by the mere presence/absence of the visual stimulation. Results: Condition-specific single-epoch SSVEPs and fMRI responses were observed at occipital sites. Combined SSVEPs–fMRI analysis at the single-epoch level did not reveal any significant correlation between the two recordings. However, both signals contained stimulation-specific linear decreases that may relate to neuronal habituation. Conclusions: Our findings demonstrate robust estimation of single-epoch evoked potentials and fMRI responses during interleaved recording, using visual steady-state stimulation. Significance: Single-epochs analysis of evoked potentials and fMRI signals is feasible for interleaved SSVEPs–fMRI recordings.

Functional magnetic resonance imaging (fMRI) has emerged during the last decade as the main non-invasive technique for the investigation of human brain function. More recently, fMRI was also proposed for functional studies of the human spinal cord, but with controversial results. In fact, the functional contrast is not well-characterized, and even its origin has been challenged. In the present work, we characterized the temporal features of the functional signal evoked in the human spinal cord by a motor task, studied with an approach based on time-locked averaging of functional time series of different durations. Based on the results here reported, we defined an impulse-response function (irf) able to explain the functional response for motor tasks in the interval of 15-42 s of duration, thus suggesting the linearity of the phenomenon in this interval. Conversely, with stimulation durations ranging between 3 and 9 s, the functional signal was not detectable, and was under the level predicted by a linear behavior, suggesting deviation from linearity during short stimulations. The impulse-response function appeared slower than in the brain, peaking at about 9 s after its beginning. The observed contrast was generally larger than in the brain, on the order of about 5.4% of baseline signal at 1.5 T. The findings further suggested that the physiological origin of T(2) weighted functional imaging is similar in the spinal cord and in the brain.

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in neural activity are accompanied by modulation in the blood-oxygenation-level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed in many fMRI experiments, which show regions of cortex that seem to respond in antiphase with primary stimulus. The existence of this so-called negative BOLD response (NBR) has been observed and investigated in many functional studies. Several theoretical mechanisms have been proposed to account for it, but its origin has never been fully explained. In this study, the variability of fMRI activation, including the sources of the negative BOLD signal, during phonological and semantic language tasks. was investigated in six right-handed healthy subjects. We found significant activations in the brain regions, mainly in the left hemisphere, involved in the language stimuli [prominent in the inferior frontal gyrus, approximately Brodmann Areas (BA)7, BA44, BA45 and BA47, and in the precuneus]. Moreover, we observed activations in motor regions [precentral gyrus and supplementary motor area (SMA)], a result that suggests a specific role of these areas (particularly the SMA) in language processing. Functional analysis have also shown that certain brain regions, including the posterior cingulate cortex and the anterior cingulate cortex, have consistently greater activity during resting states compared to states of performing cognitive tasks. In our study, we observed diffuse NBR at the cortical level and a stronger negative response in correspondence to the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in hemodynamics. We discussed about the importance of these responses that are anticorrelated with the stimulus. Our data suggest that particular care must be considered in the interpretation of fMRI findings, especially in the case of presurgical studies. (c) 2007 Elsevier Inc. All rights reserved.

Patients with drug-resistant focal epilepsy may require intracranial investigations with subdural electrodes. These must be correctly localized with respect to the brain cortical surface and require appropriate monitoring. For this purpose, coregistration techniques, which fuse preimplantation 3D magnetic resonance imaging scans with postimplantation computed tomography scans, have been implemented. In order to reduce localization errors due to the fusion process, we used a coregistration method based on the maximization of mutual information (MI) in 11 patients with extratemporal epilepsy who were invasively investigated. Our registration method is based on three processing steps: rigid-body transformation for coregistration, computation of MI as a similarity measure and the use of the Downhill Simplex optimization method. After consistency analysis, the shift of the registration method reached 0.14+/-0.27 mm in translation and 0.03+/-0.14 degrees in rotation, and the accuracies assessed on voxels of skull surface and voxels of the center of the brain volume were 1.42+/-0.61 and 1.15+/-0.53 mm, respectively. The accuracy of the fusion process reached submillimeter range, and results were considered reliable for surgical planning in all studied patients.

There is a growing interest in combining EEG and (f)MRI data as they provide complementary information: EEG is characterized by a high temporal resolution but poor spatial one, while fMRI is characterized by a high spatial resolution but low temporal one. However, while a standard file format for storing EEG data is available since over a decade, it does not fulfill the needs of modern protocols and devices such as those involved in simultaneous EEG and fMRI recordings. The main reasons are the limited bit resolution, some difficulties encountered in handling and storing acquisition events or trace markers for off-line analyses and the impossibility to add some protocol-specific information that is not considered in the actual data formats. This, among others, hinders the release of free analysis software and makes it difficult to share data across different laboratories as every research unit develops its own tools according to its needs, stores data in proprietary formats and a lot of time is spent building software applications for converting data from one format to another. The NPX (NeuroPhysiological signals in eXtensible Markup Language) data format was defined to overcome these and other limitations, and here its main characteristics are reported as well as how some typical problems occurring in simultaneous EEG-fMRI recordings are also treated. Many tools based on the NPX technology can be freely downloaded, including a tool for removing artifacts occurring during simultaneous EEG-fMRI recordings.

Interest about simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data acquisition has rapidly increased during the last years because of the possibility that the combined method offers to join temporal and spatial resolution, providing in this way a powerful tool to investigate spontaneous and evoked brain activities. However, several intrinsic features of MRI scanning become sources of artifacts on EEG data. Noise sources of a highly predictable nature such as those related to the pulse MRI sequence and those determined by magnetic gradient switching during scanning do not represent a major problem and can be easily removed. On the contrary, the ballistocardiogram (BCG) artifact, a large signal visible on all EEG traces and related to cardiac activity inside the magnetic field, is determined by sources that are not fully stereotyped and causing important limitations in the use of artifact-removing strategies. Recently, it has been proposed to use independent component analysis (ICA) to remove BCG artifact from EEG signals. ICA is a statistical algorithm that allows blind separation of statistically independent sources when the only available information is represented by their linear combination. An important drawback with most ICA algorithms is that they exhibit a stochastic behavior: each run yields slightly different results such that the reliability of the estimated sources is difficult to assess. In this preliminary report, we present a method based on running the FastICA algorithm many times with slightly different initial conditions. Clustering structure in the signal space of the obtained components provides us with a new way to assess the reliability of the estimated sources.

The aim of the present study was to analyze blood oxygenation level-dependent (BOLD) signal variation during an apnea-based task in order to assess the capability of a functional magnetic resonance imaging (MRI) procedure to estimate cerebral vascular dynamic effects. We measured BOLD contrast by hierarchical cluster analysis in healthy subjects undergoing an fMRI experiment, in which the task paradigm was one phase of inspirational apnea (IA). By processing the time courses of the fMRI experiment, analysis was performed only on a subclass of all the possible signal patterns; basically, root mean square and absolute variation differences have been calculated. Considering the baseline value obtained by computing the mean value of the initial rest period as reference, particular voxels showed relative important variations during the IA task and during the recovery phase following the IA. We focused our interest on the signal response of voxels that would correspond mainly to white and gray matter regions and that also may be affected by the proximity of large venous vessels. The results are presented as maps of space-temporal distribution of time series variations with two levels of hierarchical clustering among voxels with low to high initial response. Furthermore, we have presented a clustering of the signal response delay, conducting to a partition and identification of specified brain sites. (c) 2006 Elsevier Inc. All rights reserved.

Simultaneous EEG-fMRI is a powerful tool to study spontaneous and evoked brain activity because of the complementary advantages of the two techniques in terms of temporal and spatial resolution. In recent years, a significant number of scientific works have been published on this subject. However, many technical problems related to the intrinsic incompatibility of EEG and MRI methods are still not fully solved. Furthermore, simultaneous acquisition of EEG and event-related fMRI requires precise synchronization of all devices involved in the experimental setup. Thus, timing issue must be carefully considered in order to avoid significant methodological errors. The aim of the present work is to highlight and discuss some of technical and methodological open issues associated with the combined use of EEG and fMRI. These issues are presented in the context of preliminary data regarding simultaneous acquisition of event-related evoked potentials and BOLD images during a visual odd-ball paradigm.

The aim of our work was to evaluate the feasibility of in vivo single-voxel quantitative proton MR spectroscopy in order to identify possible alterations in the main metabolite concentrations due to some metabolic dysfunctions in the cerebellum of patients suffering from a particular form of migraine called “with aura.” Measurements of metabolite levels in the cerebellum disclosed reduced choline values (normalized both to N-acetyl-aspartate and creatine) in the patient group with respect to the age-matched control group. Our interest in this pathology is motivated by the fact that there are no available specific biochemical markers for migraine characterization, and the current diagnostic only takes advantage of the medical history and the clinical examination.

The metabolic events underlying neuronal activity still remain the object of intense debate, in spite of the considerable amount of information provided from different experimental techniques. Indeed, several attempts at linking the cellular metabolic phenomena with the macroscopic physiological changes have not yet attained foolproof conclusions. The difficulties in drawing definitive conclusions are due primarily to the heterogeneity of the experimental procedures used in different laboratories, and also given the impossibility of extrapolating the findings obtained under stationary conditions (prolonged stimulation) to dynamic and transient phenomena. Recently, lactate has received much attention, following its proposal by Pellerin and Magistretti (1994; Proc. Natl. Acad. Sci. USA 91:10625-10629), instead of glucose, as the main substrate for neurons during activity. Several challenging aspects suggest the return to a more conventional view of neuronal metabolism, in which neurons are able to metabolize ambient glucose directly as their major substrate, also during activation.

doi:10.1016/j.pscychresns.2005.05.001 DOI of original article: 10.1016/j.pscychresns.2005.02.001. * Corresponding author. Fig. 1. Functional MR images show premotor cortex and SMA (arrows) voxels activated by little finger, unusual (on left side) and index, usua (on right side) tapping motor tasks in a control subject (top) and in a Tourette’s syndrome (TS) patient (bottom). In the control patient, the SMA is markedly activated in the unusual task; in the TS patient, similar SMA activation is observed in both the usual and unusual tasks. www.elsevier.com/locate/psychresns

A murine anti-human melanoma monoclonal antibody fragment was labeled with gadolinium and its proton relaxation efficiency compared to controls at frequencies ranging from 2 to 300 MHz. Relaxation time variations were about 30-40% in 10-15 microM solutions. The labeled fragment showed proton relaxation enhancement relative to free gadolinium, while preserving its immunoreactivity. A tentative labeling of a melanoma pellet by means of the fragment, just at the borderline of a minimum expected T1 variation, gave no detectable difference.