Functional MRI in symptomatic proliferative angiopathies

Seizures, the main expression of cerebral arteriovenous malformations (AVMs) can be difficult to control medically. We studied fMRI in correlation with clinical findings cerebral activation clusters patterns in relation with singular AVMs (proliferative angiopathy). We carried out blood oxygen-level dependent functional MRI (fMRI) in seven patients with language problems due to capillary ectasia with verbal fluency and repetition language tasks in box-car paradigms. fMRI maps were calculated with cross-correlation coefficients and superimposed on brain anatomy. Five patients had perimalformative and/or contralateral areas of ipsi- and contralateral activation clusters redistribution. One patient who underwent fMRI after a severe focal post-ictal deficit had total hemisphere contralateral activation clusters redistribution.     

Real-time multiple linear regression for fMRI supported by time-aware acquisition and processing.

Real-time parametric statistical analysis of functional MRI (fMRI) data would potentially enlarge the scope of experimentation and facilitate its application to clinical populations. A system is described that addresses the need for rapid analysis of fMRI data and lays the foundation for dealing with problems that impede the application of fMRI to clinical populations. The system, I/OWA (Input/Output time-aWare Architecture), combines a general architecture for sampling and time-stamping relevant information channels in fMRI (image acquisition, stimulation, subject responses, cardiac and respiratory monitors, etc.) and an efficient approach to manipulating these data, featuring incremental subsecond multiple linear regression. The advantages of the system are the simplification of event timing and efficient and unified data formatting. Substantial parametric analysis can be performed and displayed in real-time. Immediate (replay) and delayed off-line analysis can also be performed with the same interface. The capabilities of the system are demonstrated in normal subjects using a polar visual angle phase mapping paradigm. The system provides a time-accounting infrastructure that readily supports standard and innovative approaches to fMRI. Magn Reson Med 45:289-298, 2001.     

Clinical applicability of functional MRI

Functional MRI (fMRI) has become the most widely used modality for examining human brain function in basic and clinical neuroscience. As compared to the application of fMRI in basic neuroscience research, clinical fMRI presents unique challenges. A growing body of literature supports the feasibility of clinical fMRI, with the best-studied applications being localization of motor cortex and lateralization of language. While it may be tempting to assume that fMRI will supercede prior approaches, it may turn out that fMRI will be used to complement more difficult or invasive methods rather than replace them entirely. This article focuses on fMRI studies in patients and patient populations. Specific considerations for such applications include pathophysiological effects on functional physiology, brain-behavior correlations in the presence of cognitive or sensorimotor deficits, and test-retest reliability for longitudinal studies.     

Presurgical planning for tumor resectioning

Since the birth of functional magnetic resonance imaging (fMRI)-a noninvasive tool able to visualize brain function-now 15 years ago, several clinical applications have emerged. fMRI follows from the neurovascular coupling between neuronal electrical activity and cerebrovascular physiology that leads to three effects that can contribute to the fMRI signal: an increase in the blood flow velocity, in the blood volume and in the blood oxygenation level. The latter effect, gave the technique the name blood oxygenation level dependent (BOLD) fMRI. One of the major clinical uses is presurgical fMRI in patients with brain abnormalities. The goals of presurgical fMRI are threefold: 1) assessing the risk of neurological deficit that follows a surgical procedure, 2) selecting patients for invasive intraoperative mapping, and 3) guiding of the surgical procedure itself. These are reviewed here. Unfortunately, randomized trials or outcome studies that definitively show benefits to the final outcome of the patient when applying fMRI presurgically have not been performed. Therefore, fMRI has not yet reached the status of clinical acceptance. The final purpose of this article is to define a roadmap of future research and developments in order to tilt pre-surgical fMRI to the status of clinical validity and acceptance.     

Functional MRI with simultaneous EEG recording: feasibility and application to motor and visual activation

The possibility of combining the high spatial resolution of functional magnetic resonance imaging (fMRI) with the high temporal resolution of electroencephalography (EEG) may provide a new tool in cognitive neurophysiology, as well as in clinical applications such as epilepsy. However, the simultaneous recording of EEG and fMRI raises important practical problems: 1) the patients' safety, in particular the risk of skin burns due to electrodes heating; 2) the impairment of the EEG recording by the static magnetic field, as well as by RF and magnetic field gradients used during MRI; and 3) the quality of MR images, which may be affected by the presence of conductors and electronic devices in the MRI bore. Here we present our experiences on 19 normal volunteers who underwent combined fMRI and 16-channel EEG examination. Consistent with previous reports, safety could be assured when performing EEG recordings during fMRI acquisition. Electrophysiological signals recorded with surface EEG were similar inside and outside the 1.5 T magnet. Furthermore, fMRI using motor or visual tasks revealed similar areas of activation when performed with and without 16-channel EEG recording. J. Magn. Reson. Imaging 2001;13:943-948.     

The role of fMRI in drug discovery

Pharmacological functional (phMRI) studies are making a significant contribution to our understanding of drug-effects on brain systems. Pharmacological fMRI has an additional contribution to make in the translation of disease models and candidate compounds from preclinical to clinical investigation and in the early clinical stages of drug development. Here it can demonstrate a proof-of-concept of drug action in a small human cohort and thus contribute substantially to decision-making in drug development. We review the methods underlying pharmacological fMRI studies and the links that can be made between animal and human investigations. We discuss the potential fMRI markers of drug effect, experimental designs and caveats in interpreting hemodynamic fMRI data as reflective of changes in neuronal activity. Although there are no current published examples of fMRI applied to novel compounds, we illustrate the potential of fMRI across a range of applications and with specific reference to processing of pain in the human brain and pharmacological analgesia. Pharmacological fMRI is developing to meet the neuroscientific challenges. Electrophysiological methods can be used to corroborate the drug effects measured hemodynamically with fMRI. In future, pharmacological fMRI is likely to extend to examinations of the spinal cord and into pharmacogenetics to relate genetic polymorphisms to differential responses of the brain to drugs.     

Diagnostic functional MRI: illustrated clinical applications and decision-making

Functional magnetic resonance imaging (fMRI) has become a popular research tool, yet its use for diagnostic purposes and actual treatment planning has remained less widespread. The literature yields rather sparse evidence-based data on clinical fMRI applications and accordant decision-making. Notwithstanding, blood oxygenation level dependent (BOLD)- and arterial spin labeling (ASL)-fMRI can be judiciously combined with perfusion measurements, electroencephalographic (EEG) recordings, diffusion-weighted imaging (DWI), and fiber tractographies to assist clinical decisions. In this article we provide an overview of clinical fMRI applications based on illustrative examples. Assessment of cochlear implant candidates by fMRI is covered in some detail, and distinct reference is made to particular challenges imposed by brain tumors, other space-occupying lesions, cortical dysplasias, seizure disorders, and vascular malformations. Specific strategies, merits, and pitfalls of analyzing and interpreting diagnostic fMRI studies in individual patients are highlighted.     

Real-time functional MRI: development and emerging applications.

Real-time functional magnetic resonance imaging (fMRI) is an emerging technique for assessing the dynamic and robust changes in brain activation during an ongoing experiment. Real-time fMRI allows measurement of several processes within the brain as they occur. The extracted information can be used to monitor the quality of acquired data sets, serve as the basis for neurofeedback training, and manipulate scans for interactive paradigm designs. Although more work is needed, recent results have demonstrated a variety of potential applications for real-time fMRI for research and clinical use. We discuss these developments and focus on methods enabling real-time analysis of fMRI data sets, novel research applications arising from these approaches, and potential use of real-time fMRI in clinical settings.     

Clinical applications of functional magnetic resonance imaging

Despite its immediate success as a tool for basic research, the clinical application of functional MRI(fMRI) is still limited. FMRI has proven useful for presurgical functional mapping of the eloquent cortices. Localization of the sensorimotor cortex by fMRI may be of relatively limited value because the sensorimotor cortex can often be readily localized by means of anatomical methods. In contrast, the language cortices may not be localized anatomically and the language dominant hemisphere has been determined by invasive Wada test. Previous reports have shown that fMRI can be a promising alternative to the Wada test. A recent clinical trial has suggested that fMRI can be used to diagnose Alzheimer's disease in its earliest stage, detecting subclinical deterioration of the memory function. FMRI may be useful to predict the future decline of memory in people with genetic risks. Monitoring of the functional recovery of post-stroke brains may be another promising clinical application of fMRI. FMRI has demonstrated functional reorganization of the brain that may be related to the restoration of motor and language functions.     

Implementations of clinical functional magnetic resonance imaging using character-based paradigms for the prediction of Chinese language dominance

PURPOSE: Recently, functional MRI (fMRI) using word generation (WG) tasks has been shown to be effective for mapping the Chinese language-related brain areas. In clinical applications, however, patients' performance cannot be easily monitored during WG tasks. In this study, we evaluated the feasibility of a word choice (WC) paradigm in the clinical setting and compared the results with those from WG tasks. METHOD: Intrasubject comparisons of fMRI with both WG and WC paradigms were performed on six normal human subjects and two tumor patients. Subject responses in the WC paradigm, based on semantic judgments, were recorded. Activation strength, extent, and laterality were evaluated and compared. RESULTS: Our results showed that fMRI with the WC paradigm evoked weaker neuronal activation than that with the WG paradigm in Chinese language-related brain areas. It was sufficient to reveal language laterality for clinical use, however. In addition, it resulted in less nonlanguage-specific brain activation. CONCLUSION: Results from the patient data demonstrated strong evidence for the necessity of incorporating response monitoring during fMRI studies, which suggested that fMRI with the WC paradigm is more appropriate to be implemented for the prediction of Chinese language dominance in clinical environments.     

Pitfalls in fMRI

Several different techniques allow a functional assessment of neuronal activations by magnetic resonance imaging (fMRI). The by far most influential fMRI technique is based on a local T2*-sensitive hemodynamic response to neuronal activation, also known as the blood oxygenation level dependent or BOLD effect. Consequently, the term ‘fMRI’ is often used synonymously with BOLD imaging. Because interpretations of fMRI brain activation maps often appear intuitive and compelling, the reader might be tempted not to critically question the fundamental processes and assumptions. We review some essential processes and assumptions of BOLD fMRI and discuss related confounds and pitfalls in fMRI – from the underlying physiological effect, to data acquisition, data analysis and the interpretation of the results including clinical fMRI. A background framework is provided for the systematic and critical interpretation of fMRI results.     

The clinical potential of functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) has had a huge impact on understanding the healthy human brain. To date it has had much less impact in clinical neuroscience or clinical practice. The reasons for this are in part that the image acquisition, paradigm design, and data analysis strategies used presently are not sufficiently standardized. This makes the comparison of results across individuals, scanning sessions, and centers difficult. Nevertheless, there are emerging applications for clinical fMRI, and as the field matures the number of applications is likely to grow. It seems certain that fMRI has an important role to play in helping us understand the mechanisms of neuropsychiatric diseases and in helping to identify effective therapeutic strategies.     

Combining EEG and fMRI: a multimodal tool for epilepsy research

Patients with epilepsy often present in their electroencephalogram (EEG) short electrical potentials (spikes or spike-wave bursts) that are not accompanied by clinical manifestations but are of important diagnostic significance. They result from a population of abnormally hyperactive and hypersynchronous neurons. It is not easy to determine the location of the cerebral generators and the other brain regions that may be involved as a result of this abnormal activity. The possibility to combine EEG recording with functional MRI (fMRI) scanning opens the opportunity to uncover the regions of the brain showing changes in the fMRI signal in response to epileptic spikes seen in the EEG. These regions are presumably involved in the abnormal neuronal activity at the origin of epileptic discharges. This paper reviews the methodology involved in performing such studies, particularly the challenge of recording a good quality EEG inside the MR scanner while scanning is taking place, and the methods required for the statistical analysis of the combined EEG and fMRI time series. We review the results obtained in patients with different types of epileptic disorders and discuss the difficult theoretical problems raised by the interpretation of an increase (activation) and decrease (deactivation) in blood oxygen level dependent (BOLD) signal, both frequently seen in response to spikes.     

Future prospects for fMRI in the clinic

Functional MRI (fMRI) has tremendous clinical potential that is as yet unrealized. There are tremendous unmet medical needs that fMRI could address with significant benefit to human health. However, both medical and technical barriers prevent this benefit from accruing today. Technical barriers may be the reflexive focus of the current practitioners of fMRI, a technically savvy group. However, the real challenge lies in the medical realm, and this will require multidisciplinary and interdisciplinary work since the technical aspects of fMRI are ahead of the medical aspects. This can be seen in a range of diseases from Alzheimer's disease to schizophrenia to ischemic stroke: in each case our ability to image changes with fMRI outstrips our ability to do anything useful for the patient with them. Diagnostic imaging will always be linked in the clinic to therapeutic choices, and therefore the most powerful approach to link fMRI more directly to the clinic will be to tie fMRI to therapy development and implementation.     

运动皮层区域病变的功能磁共振成像研究及应用

功能磁共振成像是近年来新兴的脑功能成像技术。对运动皮层区域病变的研究是其主要临床应用之处,尤其在该区域占位性病变的术前定位,病变与脑功能区的内在联系及运动皮层的可塑性研究等方面得到了较大的发展。本文就fMRI在运动区域病变中的临床应用及进展方面作一综述。     

Comparison of fMRI coregistration results between human experts and software solutions in patients and healthy subjects

Functional magnetic resonance imaging (fMRI) performed by echo-planar imaging (EPI) is often highly distorted, and it is therefore necessary to coregister the functional to undistorted anatomical images, especially for clinical applications. This pilot study provides an evaluation of human and automatic coregistration results in the human motor cortex of normal and pathological brains. Ten healthy right-handed subjects and ten right-handed patients performed simple right hand movements during fMRI. A reference point chosen at a characteristic anatomical location within the fMRI sensorimotor activations was transferred to the high resolution anatomical MRI images by three human fMRI experts and by three automatic coregistration programs. The 3D distance between the median localizations of experts and programs was calculated and compared between patients and healthy subjects. Results show that fMRI localization on anatomical images was better with the experts than software in 70% of the cases and that software performance was worse for patients than healthy subjects (unpaired t-test: P = 0.040). With 45.6 mm the maximum disagreement between experts and software was quite large. The inter-rater consistency was better for the fMRI experts compared to the coregistration programs (ANOVA: P = 0.003). We conclude that results of automatic coregistration should be evaluated carefully, especially in case of clinical application.     

Frontiers of brain mapping using MRI

Over the past dozen years, the use of MRI techniques to map brain function (fMRI) has sparked a great deal of research. The ability of fMRI to image several different physiological processes concurrently (i.e., blood oxygenation, blood flow, metabolism) and noninvasively over large volumes make it the ideal choice for many different areas of neuroscience research in addition to countless applications in clinical settings. Furthermore, with the advent of high magnetic fields (and other hardware advancements, i.e., parallel imaging) for both human and animal research, spatial and temporal resolutions continue to be pushed to higher levels because of increases in the sensitivity as well as specificity of MR-detectable functional signals. fMRI methodology continues to grow and has the ability to cater to many different research applications. There seems to be no foreseeable end in sight to the advancement of fMRI techniques and its subsequent use in basic research as well as in clinical settings. In this work, fMRI techniques and the ongoing development of existing techniques are discussed with implications for the future of fMRI.     

Presurgical Functional Magnetic Resonance Imaging (fMRI)

Abstract Preoperative functional magnetic resonance imaging (fMRI) permits noninvasive measurement, localization and lateralization of important functions of the human brain in patients with brain tumors, facilitating selection of the least harmful treatment and surgery which preserves function. Preoperative fMRI of motor and language function can be performed when reliably proven clinical imaging protocols are used. Standardization of the respective imaging procedures is essential to the diagnostic use of fMRI. However, fMRI cannot be considered a fully established method of diagnostic neuroimaging due to a lack of recommendations or guidelines from the relevant medical associations, and also the lack of medical licensing of important hardware and software components. This article reviews current research in the field and provides the reader with the practical information necessary to perform presurgical fMRI.      

Functional MRI activation of somatosensory and motor cortices in a hand-grafted patient with early clinical sensorimotor recovery

The aim of this study was to investigate somatosensory and motor cortical activity with functional MRI (fMRI) in a hand-grafted patient with early clinical recovery. The patient had motor fMRI examinations before transplantation, and motor and passive tactile stimulations after surgery. His normal hand and a normal group were studied for comparison. A patient with complete brachial plexus palsy was studied to assess the lack of a fMRI signal in somatosensory areas in the case of total axonal disconnection. Stimulating the grafted hand revealed significant activation in the contralateral somatosensory cortical areas in all fMRI examinations. The activation was seen as early as 10 days after surgery; this effect cannot be explained by the known physiological mechanisms of nerve regeneration. Although an imagination effect cannot be excluded, the objective clinical recovery of sensory function led us to formulate the hypothesis that a connection to the somatosensory cortex was rapidly established. Additional cases and fundamental studies are needed to assess this hypothesis, but several observations were compatible with this explanation. Before surgery, imaginary motion of the amputated hand produced less intense responses than executed movements of the intact hand, whereas the normal activation pattern for right-handed subjects was found after surgery, in agreement with the good clinical motor recovery.     

EEG-triggered functional MRI in patients with pharmacoresistant epilepsy

Functional magnetic resonance imaging (fMRI) triggered by scalp electroencephalography (EEG) recordings has become a promising new tool for noninvasive epileptic focus localization. Studies to date have shown that it can be used safely and that highly localized information can be obtained. So far, no reports using comprehensive clinical information and/or long-term follow-up after epilepsy surgery in a larger patient group have been given that would allow a valuable judgment of the utility of this technique. Here, the results of 11 patients with EEG-triggered fMRI exams who also underwent presurgical evaluation of their epilepsy are given. In most patients we were able to record good quality EEG inside the magnet, allowing us to trigger fMRI acquisition by interictal discharges. The fMRI consisted of echoplanar multislice acquisition permitting a large anatomical coverage of the patient's brain. In 8 of the 11 patients the exam confirmed clinical diagnosis, either by the presence (n = 7) or absence (n = 1) of focal signal enhancement. In six patients, intracranial recordings were carried out, and in five of them, the epileptogenic zone as determined by fMRI was confirmed. Limitations were encountered a) when the focus was too close to air cavities; b) if an active epileptogenic focus was absent; and c) if only reduced cooperation with respect to body movements was provided by the patient. We conclude that EEG-triggered fMRI is a safe and powerful noninvasive tool that improves the diagnostic value of MRI by localizing the epileptic focus precisely.