Composition and dynamics of articular cartilage: structure, function, and maintaining healthy state

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD-fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word-stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient-refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated.     

Three-dimensional anisotropy contrast (3DAC) magnetic resonance imaging of the human brain: application to assess Wallerian degeneration

Three-dimensional anisotropy contrast (3DAC) magnetic resonance imaging is a new algorithm for the treatment of apparent diffusion tensor using the three primary colors. To determine if 3DAC has a clinical application for human brain, six normal volunteers and twenty patients with supratentorial cerebrovascular accidents were examined using clinical magnetic resonance imaging (MRI), and the changes in the 3DAC images associated with Wallerian degeneration of the pyramidal tract were evaluated. The 3DAC images exhibited impressive anatomical resolution. In all chronic stage patients with hemiparesis, the colors in the pyramidal tract were faded. Patients examined during the acute stage who later recovered from hemiparesis had no visible changes of the 3DAC image, whereas patients who recovered poorly showed distinct color fading in the pyramidal tract within 14 days following stroke. In conclusion, very fine anatomical structures are visible on 3DAC images, and it can be used as a diagnostic tool for the human brain.     

Theory and clinical application of functional MRI: 3D-functional brain mapping

Functional magnetic resonance imaging (fMRI) was performed using a clinical 1.5 T MR scanner. Normal volunteers and patients with several neurological disorders were studied with somatosensory stimulation using sponge at right hand and visual stimulation using checkerboard pattern. Both fMR images by gradient echo echo planar imaging and three dimensional gradient echo images were studied. Reconstructed 3 dimensional functional brain mapping was superimposed on 3D anatomical images. Apparent signal increase was observed at contra lateral sensorimotor cortex and secondary sensory cortex with sponge stimulation. In the case of left homonymous hemianopia due to cerebral infarction, increasing signal was only observed surrounding left calcarine fissure by using stimulation of all visual field. In conclusion, fMRI and 3-D functional brain mapping has extremely high potentiality to examine pathophysiology of various neurological disorders.     

Experiences with functional magnetic resonance imaging at 1 tesla

Functional magnetic resonance imaging (fMRI) has been performed on a standard 1 T system using a pulse sequence developed to utilize blood oxygen level dependent (BOLD) contrast and an off-line analysis routine using correlation techniques. The sequence and the data analysis routine have been validated by reproducing the conventional hand movement paradigm studies reported by numerous other workers. Our work has then been extended to investigate cerebral foci for a tonic pain stimulus and the cortical representation of oesophageal stimulation. Both these studies relate to paradigms where the expected BOLD signal is significantly less than that encountered for motor or visual cortex paradigms. The results show good agreement with other modalities (positron emission tomography, magnetoencephalography and cortical evoked potentials). Performing fMRI at 1 T is slightly controversial. However, our successful study of demanding paradigms, using a standard clinical 1 T imaging system, has important implications for many other users operating at this field strength.     

Analysis of dynamic brain imaging data

Modern imaging techniques for probing brain function, including functional magnetic resonance imaging, intrinsic and extrinsic contrast optical imaging, and magnetoencephalography, generate large data sets with complex content. In this paper we develop appropriate techniques for analysis and visualization of such imaging data to separate the signal from the noise and characterize the signal. The techniques developed fall into the general category of multivariate time series analysis, and in particular we extensively use the multitaper framework of spectral analysis. We develop specific protocols for the analysis of fMRI, optical imaging, and MEG data, and illustrate the techniques by applications to real data sets generated by these imaging modalities. In general, the analysis protocols involve two distinct stages: "noise" characterization and suppression, and "signal" characterization and visualization. An important general conclusion of our study is the utility of a frequency-based representation, with short, moving analysis windows to account for nonstationarity in the data. Of particular note are 1) the development of a decomposition technique (space-frequency singular value decomposition) that is shown to be a useful means of characterizing the image data, and 2) the development of an algorithm, based on multitaper methods, for the removal of approximately periodic physiological artifacts arising from cardiac and respiratory sources.     

Comparison of functional MR-venography and EPI-BOLD fMRI at 1.5 T

Functional magnetic resonance imaging (fMRI) of the brain using blood oxygenation level dependent (BOLD) contrast relies on the changes of paramagnetic deoxyhemoglobin concentration, which affects brain parenchyma and draining venous vessels. These changes in deoxyhemoglobin concentration in venous vessels can also be monitored using a high-resolution susceptibility-based MR-venography technique. Four volunteers participated in the study in which functional MR-venograms were compared with conventional echo-planar imaging (EPI)-BOLD-fMRI. In all cases, small venous vessels could be identified close to the areas of activation detected by conventional fMRI. In the venograms, task performance (finger tapping) resulted in a loss of venous vessel contrast compared to the resting state, which is consistent with a local decrease of deoxyhemoglobin concentration. MR-venography allows a direct visualization of the BOLD-effect at high spatial resolution. In combination with conventional fMRI, this technique may help to separate the contribution of brain parenchyma and venous vessels in fMRI studies.     

Changes in fMRI Following Cognitive Rehabilitation in Severe Traumatic Brain Injury: A Case Study.

Objective: To illustrate the relationship between changes in neuropsychological testing and changes in functional magnetic resonance imaging (fMRI) before and after cognitive rehabilitation therapy (CRT). Study Design: Single case study. Setting: Outpatient treatment center. Participant: A woman with history of severe traumatic brain injury (TBI) 16 years before study. Intervention: Individualized CRT using a developmental metacognitive model. Main Outcome Measures: Neuropsychological tests and fMRI imaging performed during an eye movement task and a reading comprehension task. Results: Improvements on some neuropsychological test scores (>1 SD) and changes in the magnitude and distribution of the blood oxygen level dependent (BOLD) response as a function of task performance on both fMRI tasks. Conclusions: Individuals with severe TBI many years postinjury can demonstrate improvements in neuropsychological testing following CRT. Behavioral improvements can be related to changes in brain activity using fMRI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional mapping of pain-related activation with echo-planar MRI: significance of the SII-insular region

Activation in numerous regions of the brain is likely to be involved in the complex neural network function of pain perception. To detect the cortical representation during nonpainful and painful stimuli, which were presented using electrical finger stimulation in six normal right-handed male volunteers, we performed echo-planar functional magnetic resonance imaging (fMRI). Using a 1.5-T MR system that scanned the supratentorial region of the brain, we obtained multislice BOLD-based functional MR images with single-shot gradient-echo echo-planar imaging (EPI). The data show that dispersed brain regions are activated during painful stimulation, and especially demonstrate the significance of the SII-insular region in pain perception.     

A functional MRI study of human amygdala responses to facial expressions of fear versus anger.

Functional magnetic resonance imaging (fMRI) of the human brain was used to compare changes in amygdala activity associated with viewing facial expressions of fear and anger. Pictures of human faces bearing expressions of fear or anger, as well as faces with neutral expressions, were presented to 8 healthy participants. The blood oxygen-level dependent (BOLD) fMRI signal within the dorsal amygdala was significantly greater to Fear versus Anger, in a direct contrast. Significant BOLD signal changes in the ventral amygdala were observed in contrasts of Fear versus Neutral expressions and, in a more spatially circumscribed region, to Anger versus Neutral expressions. Thus, activity in the amygdala is greater to fearful facial expressions when contrasted with either neutral or angry faces. Furthermore, directly contrasting fear with angry faces highlighted involvement of the dorsal amygdaloid region. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional magnetic resonance imaging of primary visual processing using a 1.0 Tesla scanner

Recent advances in functional magnetic resonance imaging (fMRI) at > or = 1.5 T magnetic field strength and with high speed single-shot echo planar imaging techniques have made it possible to monitor local changes in cerebral blood volume, cerebral blood flow, and blood oxygenation level in response to sensory stimulation, simple motor activity, and possibly also to more complex cognitive processing. However, fMRI has also been accomplished on conventional MR scanners of medium field strength (approximately 1.0 T) using special pulse sequences and appropriate methods for image analysis. We present results from six subjects on photic stimulation using a standard 1.0 T MR scanner together with special software for off-line image analysis. Continuous serial T2-weighted imaging were performed for 6 minutes in the plane of the calcarine fissure. There were 3 repetitions of 1 minute resting state of darkness (OFF) and 1 minute activated state (ON) with 8 Hz flicker stimulation. To directly map these functional images to the underlying anatomy we also acquired a high resolution T1-weighted image from the same axial slice. The results demonstrated that stimulus-related signals can be obtained from primary visual cortex with a conventional 1.0 T MR scanner. Further methodological improvements are discussed and related to present and future possibilities for the use of fMRI within psychophysiology.     

Intensity coding of auditory stimuli: an fMRI study

The effect of stimulus intensity (sound pressure level, SPL) of auditory stimuli on the BOLD response in the auditory cortex was investigated in 14 young and healthy subjects, with no hearing abnormalities, using echo-planar, functional magnetic resonance imaging (fMRI) during a verbal and a non-verbal auditory discrimination task. The stimuli were presented block-wise at three different intensities: 95, 85 and 75 dB (SPL). All subjects showed fMRI signal increases in superior temporal gyrus (STG) covering primary and secondary auditory cortex. Most importantly, the spatial extent of the fMRI response in STG increased with increasing stimulus intensity. It is hypothesized that spreading of excitation is associated with the encoding of increasing stimulus intensity levels. In addition, we found bifrontal activation supposedly evoked by the auditory-articulary loop of working memory. The results presented here should assist in the design of optimal activation strategies for studying the auditory cortex with fMRI paradigms and may help in understanding intensity coding of auditory stimuli.     

Facial affect recognition training in autism: Can we animate the fusiform gyrus?

One of the most consistent findings in the neuroscience of autism is hypoactivation of the fusiform gyrus (FG) during face processing. In this study the authors examined whether successful facial affect recognition training is associated with an increased activation of the FG in autism. The effect of a computer-based program to teach facial affect identification was examined in 10 individuals with high-functioning autism. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) changes in the FG and other regions of interest, as well as behavioral facial affect recognition measures, were assessed pre- and posttraining. No significant activation changes in the FG were observed. Trained participants showed behavioral improvements, which were accompanied by higher BOLD fMRI signals in the superior parietal lobule and maintained activation in the right medial occipital gyrus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlating MR lesions and functional deficits in multiple sclerosis patients. Anatomical atlas registration

Although brain magnetic resonance (MR) imaging is increasingly being used as an objective outcome measure in treatment trials for multiple sclerosis (MS), findings correlating conventional MR imaging and disabilities in established MS have been inconsistent. In some studies, measures of MR lesion status, such as numbers of lesions or MS lesion load (volume), have shown limited correlations with clinical scores such as the Kurtzke Expanded disability scale (EDSS). Other studies have shown clear correlations between MR findings and measures of disability in MS. Further development of image processing techniques should help elucidate the relationships between MR findings and disease processes in MS.     

Mechanism and prevention of port-site tumor recurrence after laparoscopy in a murine model

Functional activation of somatosensory cortex was studied in alpha-chloralose anesthetized rats by functional magnetic resonance imaging (fMRI), using both perfusion-weighted and T2*-weighted (blood oxygenation level dependent, BOLD) imaging. The sensitivity of functional activation was altered by ventilating animals for 3 minutes with 6% CO2. Before hypercapnic conditioning, electrical stimulation of the left forepaw at a frequency of 3 Hz led to an increase of signal intensity (relative to the unstimulated baseline condition) in the right somatosensory cortex by 6+/-2% (means+/-SD) in T2*-weighted images and by 45%+/-48% in perfusion-weighted images. After hypercapnic conditioning the signal intensity increase in perfusion-weighted images doubled to 91%+/-62% (P=0.034), whereas that of T2*-weighted images only marginally increased to 7+/-4% (not significant). This different behavior in both imaging modalities is interpreted as evidence for an increased flow response in combination with a higher oxygen extraction. Thus, the fMRI data reflect hypercapnia-induced resetting of the functional-metabolic coupling of the tissue during activation.     

Determination of famotidine in human plasma by high performance liquid chromatography with column switching

While functional magnetic resonance imaging (fMRI) is now used widely for demonstrating neural activity-related signals associated with perceptual, motor, and cognitive processes in humans, to date this technique has not been developed for use with nonhuman primates. fMRI in monkeys offers a potentially valuable experimental approach for investigating brain function, which will complement and aid existing techniques such as electrophysiology and the behavioral analysis of the effects of brain lesions. There are, however, a number of significant technical challenges involved in using fMRI with monkeys. Here, we describe the procedures by which we have overcome these challenges to carry out successful fMRI experiments in an alert monkey, and we present the first evidence of activity-related fMRI signals from monkey cerebral cortex.     

'Musical brain' revealed by high-field (3 Tesla) functional MRI

The cortical areas subserving music literacy were investigated using high-field (3 Tesla) functional magnetic resonance imaging (fMRI). The activation pattern associated specifically with music score reading was compared with that associated with reading text in a subject's primary and secondary language. While the areas of activation were predominantly identical for all three reading modalities, there were areas within the occipital cortex activated exclusively by music score reading. Grand analysis of the activation patterns of eight pianists unequivocally identified that the principal cortical area needed for music literacy is the cortex flanking the right transverse occipital sulcus (musical brain).     

Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation. Short communication

Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods become available, it is important to understand their relative advantages and liabilities, as well as how the information gained compares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is to combine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in cross comparing new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations.     

Molecular pathophysiology of cystic fibrosis based on the rescued knockout mouse model

Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast has progressed rapidly and is commonly used to study function in many regions of the human brain. This paper introduces a method for characterizing the linear and nonlinear properties of the hemodynamic response. Such characterization is essential for accurate prediction of time-course behavior. Linearity of the BOLD response was examined in the primary visual cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2, 4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s duration) were used to test the hemodynamic response. Superposition of the obtained responses was performed to determine if the BOLD response is nonlinear. The nonlinear characteristics of the BOLD response were assessed using a Laplacian linear system model cascaded with a broadening function. Discrepancies between the model and the observed response provide an indirect measure of the nonlinearity of the response. The Laplacian linear system remained constant within subjects so the broadening function can be used to absorb nonlinearities in the response. The results show that visual stimulation under 4 s in duration and less than 40% contrast yield strong nonlinear responses.     

Functional magnetic resonance imaging in macaque cortex

The ability to use fMRI in a monkey model would bridge the gap between the fMRI demonstration of cerebral activation in humans and the cumulative wealth of monkey data on the functional organization of the brain from single electrode mapping, radioisotope and histology studies. We report a new technique for fMRI in an awake co-operative rhesus macaque (Macaca mulatta) in a conventional clinical 1.5T MR scanner and present the first fMRI images from a macaque. Good resolution, signal-to-noise ratio and BOLD response (2.6-4.6%) have been achieved using the manufacturer's standard volume knee coil. T1 values of macaque gray and white matter (1490 ms, 1010 ms respectively) are higher than human brain, whereas T2 values are lower (55 ms, 48 ms respectively). An MR-compatible design for restraining the monkey is also described, along with a suitable EPI sequence for BOLD images, optimized for monkey T2, with voxel sizes from 29 to 61 microl, and MPRAGE sequence for anatomical studies with 0.8 mm isotropic resolution, optimized for monkey T1.     

The SPINRPHEX club

A 3-year-old Japanese domestic cat with a diagnosis of lymphocytic leukemia showed severe generalized seizures in the course of chemotherapy after leukemic condition was improved clinically. Computed tomography (CT) and magnetic resonance (MR) imaging of the brain were carried out. Both contrast procedures disclosed enhancements at the falx cerebri and the margin of cerebral cortex. Among these procedures contrast MR imaging demonstrated the lesion most clearly. Cytological examination of cerebrospinal fluid obtained by spinal puncture showed the infiltration of malignant cells and the diagnosis of meningeal syndrome associated with lymphocytic leukemia was defined. Intrathecal administration of cytosine arabinoside partially improved the neurologic dysfunction. Autopsy and histopathological examination confirmed the infiltration of leukemic cells in the areas of meningeal lesion demonstrated with contrast CT and MR imaging. Thus these imaging techniques, especially contrast MR imaging, are useful tools for rapid and precise diagnosis of meningeal syndrome.