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Biomedical subjects

T P Roberts

Publications and source records attributed to T P Roberts.

At least 19 recordsLinked to original sources

A hemispherically asymmetrical MEG response to vowels.

Neuromagnetic fields elicited by vowels and tones were recorded and sources were modeled as single equivalent current dipoles (ECDs) in 1 ms steps 80-400 ms post stimulus. To vowels, the left hemisphere (LH) auditory cortex had nearly twice as many satisfactory ECD fits as the right hemisphere (RH). Tones did not evoke such asymmetry. In particular, in the late field (150-400 ms) the LH had more than twice as many ECDs as the RH, and the spatial distribution of LH sources was more clustered than in the RH. An asymmetrical, focal cortical mechanism for vowel processing was identified that intensified in later auditory processing stages. These data suggest that MEG might be used for non-invasive, language laterality determination with simple vowel-like stimuli.

Adult

Brain processing of capsaicin-induced secondary hyperalgesia: a functional MRI study.

OBJECTIVE: To investigate, using functional MRI (fMRI), the neural network that is activated by the pain component of capsaicin-induced secondary mechanical hyperalgesia. BACKGROUND: Mechanical hyperalgesia (i.e., pain to innocuous tactile stimuli) is a distressing symptom of neuropathic pain syndromes. Animal experiments suggest that alterations in central pain processing occur that render tactile stimuli capable of activating central pain-signaling neurons. A similar central sensitization can be produced experimentally with capsaicin. METHODS: In nine healthy individuals the cerebral activation pattern resulting from cutaneous nonpainful mechanical stimulation at the dominant forearm was imaged using fMRI. Capsaicin was injected adjacent to the stimulation site to induce secondary mechanical hyperalgesia. The identical mechanical stimulation was then perceived as painful without changing the stimulus intensity and location. Both activation patterns were compared to isolate the specific pain-related component of mechanical hyperalgesia from the tactile component. RESULTS: The pattern during nonpainful mechanical stimulation included contralateral primary sensory cortex (SI) and bilateral secondary sensory cortex (SII) activity. During hyperalgesia, significantly higher activation was found in the contralateral prefrontal cortex: the middle (Brodmann areas [BAs] 6, 8, and 9) and inferior frontal gyrus (BAs 44 and 45). No change was present within SI, SII, and the anterior cingulate cortex. CONCLUSIONS: Prefrontal activation is interpreted as a consequence of attention, cognitive evaluation, and planning of motor behavior in response to pain. The lack of activation of the anterior cingulate contrasts with physiologic pain after C-nociceptor stimulation. It might indicate differences in the processing of hyperalgesia and C-nociceptor pain or it might be due to habituation of affective sensations during hyperalgesia compared with acute capsaicin pain.

Adult

The use of fMRI for determining the topographic organization of cortical fields in human and nonhuman primates.

In this study, we demonstrate activation of somatosensory cortex in the anesthetized macaque monkey and awake human using fMRI, and confirm the topographic organization of somatosensory cortex previously described in both species. The macaque model provides an efficient means of addressing questions regarding the capabilities and neurophysiological relevance of fMRI, and serves as an interface between established invasive electrophysiological methods in nonhuman primates, and noninvasive imaging assays of functional activation in humans.

Anesthetics

MRI of acute myocardial ischemia: comparing a new contrast agent, Gd-DTPA-24-cascade-polymer, with Gd-DTPA.

A new macromolecular contrast agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, was compared with Gd-DTPA for time-dependent delineation of acute myocardial ischemia. Acute myocardial ischemia was produced in 12 rats by occluding the anterior branch of the left coronary artery for 20-40 minutes. Dynamic spin-echo magnetic resonance imaging (MRI) was performed for 30 minutes after injection of Gd-DTPA (n = 6) or the cascade polymer (n = 6) using equimolar doses (0.1 mmol of Gd/kg). The contrast agent-induced changes in signal intensity (deltaSI) in normal and ischemic myocardium were observed. In normal myocardium, both contrast agents caused a sharp increase in deltaSI, followed by a decline to baseline values over the 30-minute period. Enhancement in the ischemic myocardium was attenuated. Gd-DTPA showed greater deltaSI in ischemic myocardium than the cascade polymer, which gave rise to virtually no enhancement. Significant differences (P<0.05) in signal enhancement between normal and ischemic myocardium persisted for only 6 minutes using Gd-DTPA but for 18 minutes with the cascade polymer. Use of Gd-DTPA-24-cascade-polymer extends the temporal window of dynamic contrast-enhanced MRI for the differentiation of ischemic and normal myocardium. Identification of the ischemic zone is easier with the cascade polymer, which demonstrates virtually no signal enhancement in this territory.

Animals

Tumor blood volume assays using contrast-enhanced magnetic resonance imaging: regional heterogeneity and postmortem artifacts.

Tumor blood volume (BV), subject to both morphologic and physiologic influences, can be measured using contrast-enhanced magnetic resonance imaging (MRI). The aims of this study were to determine whether MRI enhanced with a macromolecular contrast medium (MMCM) could resolve differences in BV between different tumor types, between different regions within tumors, and within the same tumor in life and after death. Tumor BV estimates were based on the MRI signal intensity responses in the tumors and in reference venous blood following enhancement with a blood pool MMCM using two mammary adenocarcinoma models. Estimates of BV were made before and immediately following death. An in vitro measurement of tumor gadolinium concentration following death was correlated with MRI enhancement. Statistically significant differences (P < 0.05) were observed in MRI-estimated tumor BV between tumor subtypes, between in vivo and postmortem measurements, and between the tumor periphery and tumor centers. MRI assays enhanced with a macromolecular contrast agent can resolve blood volume differences between tumor types, between regions within the same tumor, and between vital and postmortem states.

Albumins

Contrast-enhanced MR imaging of two superparamagnetic RES-contrast agents: functional assessment of experimental radiation-induced liver injury.

The purpose of this study was to compare liver contrast-enhancing characteristics of two superparamagnetic reticuloendothelial system (RES)-directed agents with different particle sizes, polycrystalline iron oxide nanocompounds (PION) and carboxydextran-coated maghemite (DDM128N/389, later referred to as DDM128), in an experimental model of focal radiation-induced hepatitis. PION, for the small particle size (31 nm), and DDM128, for the large particle size (59 nm), RES-directed agents were compared for liver enhancement after radiation-induced liver injury. A single x-irradiation exposure varying from 10 to 60 Gy was delivered to one side of the liver. T2-weighted spinecho magnetic resonance imaging was performed 3 days after x-irradiation at 30 minutes post-contrast. Using the RES-directed PION, the normal, non-irradiated portion of the liver decreased in signal intensity with a maximum negative enhancement of -66%, while the irradiated portion of the liver decreased in signal intensity by -24% (60 Gy). The signal intensity decline of irradiated liver tissue using PION was dose dependent, but was found at all radiation dose levels (10-60 Gy). The difference in signal intensity between irradiated (-63%) and non-irradiated (-82%) portions was also statistically different using DDM128 at 60 Gy. However, lower irradiation doses (10 and 30 Gy) failed to produce a statistically significantly different enhancement in the irradiated and non-irradiated portion of the liver. Sensitivity of liver enhancement with RES-directed agents is size dependent. The smaller particle (PION) is more sensitive for detection of radiation-induced hepatitis than the larger particle (DDM128). The relative insensitivity of DDM128 enhancement for diffuse liver injury will be clinically advantageous for detecting focal lesions in the presence of diffuse hepatic injury.

Animals

MR imaging of the arthritic rabbit knee joint using albumin-(Gd-DTPA)30 with correlation to histopathology.

The purpose of this study was to demonstrate a technique, in a pilot study, for measuring abnormal capillary permeability in synovial tissue of rabbit arthritic knees using dynamic MRI with a gadolinium-based blood pool agent. Arthritis, simulating rheumatoid arthritis, was induced in knees of 8 rabbits by intra-articular injection of carrageenan (n = 4) or ovalbumin (n = 4). Sequential fat presaturated T1-weighted Spoiled Grass images were obtained before and up to 30 min after intravenous administration of albumin-(Gd-DTPA)30. Estimates of synovial tissue plasma-volume (PV), fractional-leak-rate (FLR), and permeability-surface-area-product (PS) were computed. Histologic correlation was obtained in the corresponding regions. Dynamic MRI showed extravasation of albumin-(Gd-DTPA)30 into hypertrophic synovium in six of the eight arthritic knees. Histologic examination of these six knees showed markedly inflamed synovium. The two knees that did not show abnormal vascular permeability contained non-hypertrophic synovium. None of the rabbits showed abnormal permeability in muscle. MRI derived microvascular characteristics (PV, FLR and PS) correlated positively (r2 = 0.51, 0.97 and 0.86) with the histology. Factors involving the structural and functional microvascular characteristics of synovial tissue can be estimated non-invasively using albumin-(Gd-DTPA)30. This technique may be useful for monitoring disease progression and treatment response in rheumatoid arthritis.

Albumins

Prostate cancer tumor grade differentiation with dynamic contrast-enhanced MR imaging in the rat: comparison of macromolecular and small-molecular contrast media--preliminary experience.

PURPOSE: To differentiate prostate cancers of different histopathologic grades with dynamic gadolinium-enhanced magnetic resonance (MR) imaging. Results with a conventional small-molecular contrast medium (CM) were compared to those with a prototypic macromolecular CM. MATERIALS AND METHODS: High- and low-grade tumors, sublines of the Dunning R3327 rat prostate cancer line, were subcutaneously implanted into the flanks of 12 male Copenhagen rats. Dynamic contrast material-enhanced MR imaging was performed with small-molecular CM and macromolecular CM at an interval of 1 day. Microvascular permeability, as estimated with the endothelial transfer coefficient, and fractional plasma volume were calculated for each tumor and each CM by means of a two-compartmental, bidirectional kinetic model. RESULTS: Mean endothelial transfer coefficient values for both macromolecular CM and small-molecular CM were significantly different between the two tumor sublines (P = .0004 and P = .01, respectively). For the high- and low-grade tumors, no overlap of values was seen with macromolecular CM, but a broad overlap was seen with small-molecular CM despite a significant difference in mean values. CONCLUSION: Dynamic contrast-enhanced MR imaging permits differentiation of histopathologic prostatic tumor types. Quantitative microvascular permeability characteristics estimated from macromolecular CM-enhanced data were significantly superior to those derived from small-molecular CM-enhanced data.

Adenocarcinoma

Analysis of intrapulmonary O(2) concentration by MR imaging of inhaled hyperpolarized helium-3.

Inhalation of hyperpolarized (3)He allows magnetic resonance imaging (MRI) of ventilated airspaces. (3)He hyperpolarization decays more rapidly when interacting with paramagnetic O(2). We describe a method for in vivo determination of intrapulmonary O(2) concentrations ([O(2)]) based on MRI analysis of the fate of measured amounts of inhaled hyperpolarized (3)He in imaged regions of the lung. Anesthetized pigs underwent controlled normoventilation in a 1.5-T MRI unit. The inspired O(2) fraction was varied to achieve different end-tidal [O(2)] fractions (FET(O(2))). With the use of a specifically designed applicator, (3)He (100 ml, 35-45% polarized) was administered at a predefined time within single tidal volumes. During subsequent inspiratory apnea, serial two-dimensional images of airways and lungs were acquired. At least once in each animal studied, the radio-frequency excitation used for imaging was doubled at constant FET(O(2)). Signal intensity measurements in regions of interest of the animals' lungs (volume range, 54-294 cm(3)), taken at two different radio-frequency excitations, permitted calculation of [O(2)] in these regions of interest. The [O(2)] fractions in the regions of interest correlated closely with FET(O(2)) (R = 0.879; P < 0.0001). O(2)-sensitive (3)He-MRI may allow noninvasive study of regional distribution of ventilation and alveolar PO(2) in the lung.

Administration, Inhalation

Diffusion MR imaging. Theory and applications.

Diffusion MR imaging provides a novel way to characterize tissues based on sensitivity to the microscope molecular motion of water. Clinical implementation requires strong, fast hardware and careful post-processing of diffusion parameters. It is important to recognize that diffusion images and derivatives such as the trace of the diffusion tensor are quite specific in reflecting the physical properties of diffusion, but are non-specific for pathology. Restricted diffusion is the earliest clinically detectable sign of ischemia, but similar diffusion changes can be seen with infection and some tumors. Diffusion MR techniques are providing new ways to study problems in oncology, epilepsy, white matter disorders, and infectious diseases, both for research and clinical applications.

Animals

Auditory evoked M100 reflects onset acoustics of speech sounds.

Magnetoencephalography (MEG) was used to investigate the response to speech sounds that differ in onset dynamics, parameterized as words that have initial stop consonants (e.g., /b/, /t/) or do not (e.g., /m/, /f/). Latency and amplitude of the M100 auditory evoked neuromagnetic field, recorded over right and left auditory cortices, varied as a function of onset: stops had shorter latencies and higher amplitudes than no-stops in both hemispheres, consistent with the hypothesis that M100 is a sensitive indicator of spectral properties of acoustic stimuli. Further, activation patterns in response to stops/no-stops differed in the two hemispheres, possibly reflecting differential perceptual processing for the acoustic-phonetic cues at the onset of spoken words.

Adult

Latency of evoked neuromagnetic M100 reflects perceptual and acoustic stimulus attributes.

The latency of components of the auditory evoked neuromagnetic field has been shown to reflect, or encode, stimulus attributes. In particular, the M100 component, occurring approximately 100 ms post stimulus onset has a latency that depends on stimulus pitch, spectral complexity and presentation level. This study used magnetoencephalography to record neuromagnetic fields evoked by presentation of two-tone complexes consisting of various proportions of 100 Hz and 1 kHz energy. These are perceived categorically, as evidenced by classification and reaction time measurements. It is found that the M100 latency also varies categorically, that is, characterized by two plateau regions with a sharp interface. Thus, we find that not only does the M100 latency reflect acoustic attributes of a stimulus, but also such perceptual characteristics.

Acoustic Stimulation

Peri-threshold encoding of stimulus frequency and intensity in the M100 latency.

Recent work has suggested that, in addition to spatial tonotopy, pitch and timbre information may be encoded in the temporal activity of the auditory cortex. Specifically, the post-stimulus latency of the maximal cortical evoked neuromagnetic field (M100 or N1m) is a function of stimulus frequency. We investigated the additional effect of varying the stimulus intensity on the M100 response. A 37-channel biomagnetometer recorded neuromagnetic fields over the temporal lobe of healthy volunteers in response to monaurally presented tones. The frequency dependence of the M100 latency remained remarkably invariant even at low stimulus intensity. Thus, for peri-threshold stimuli, frequency information appears encoded in the temporal form of the evoked response.

Acoustic Stimulation

Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor.

Macromolecular contrast medium-enhanced magnetic resonance imaging (MRI) and tumor-volume measurements were applied to monitor the effects of anti-vascular endothelial growth factor (anti-VEGF) antibody on microvascular characteristics and tumor growth of MDA-MB-435 human breast cancer cells implanted in nude rats. Administration of anti-VEGF antibody (three 1 mg doses at 3-day intervals) induced significant reductions in tumor growth rates (p < 0.05) and in MRI-assayed microvascular permeabilities (p < 0.05). Results of the study were consistent with previous observations that new microvessels formed in response to angiogenesis are hyperpermeable, and with the hypothesis that hyperpermeability is a mechanistic element in angiogenesis. Variations in tumor-vessel hyperpermeability can be measured by contrast-enhanced MRI, which may prove useful for assessing antiangiogenesis therapy.

Adenocarcinoma

Magnetoencephalography and magnetic source imaging.

Current brain imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), provide noninvasive, high-resolution images that depict fine anatomic structure and delineate pathology by control of image contrast and sensitivity to the physicochemical microenvironment. These methods, although invaluable for the identification, characterization, and localization of lesions, do not provide any assessment of the functional viability of brain tissues, nor of the spatial organization of sensory, motor, and cognitive systems. However, such additional functional information is of great significance to the clinician in the determination of treatment strategies and patient management.

Brain Mapping

Learning transfer and neuronal plasticity in humans trained in tactile discrimination.

Adult humans were unilaterally trained in a tactile discrimination task of sequentially applied multi-finger stimuli. Magnetic source imaging (MSI) was performed before and after the training to evaluate use-dependent neuronal plasticity. All subjects showed fast improvements in performance and complete transfer of the learned task. MSI recordings revealed an unilateral decrease in current dipole strength in the somatosensory system contralateral to the trained hand. Attenuation of sensory evoked fields and a complete learning transfer indicate learning in associative and secondary cortices rather than perceptual plasticity operating on neuronal populations involved in early sensory processing. This findings are discussed with respect to an equivalent animal model and to learning specificity and generalization.

Adult