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T P Roberts

Publications and source records attributed to T P Roberts.

At least 19 recordsLinked to original sources

A MRI spatial mapping technique for microvascular permeability and tissue blood volume based on macromolecular contrast agent distribution.

A rapid and automated method for two-dimensional spatial depiction (mapping) of quantitative physiological tissue characteristics derived from contrast enhanced MR imaging was developed and tested in disease models of cancer, inflammation, and myocardial reperfusion injury. Specifically, an established two-compartment kinetic model of unidirectional mass transport was implemented on a pixel-by-pixel basis to generate maps of tissue permeability surface area product (PS) and fractional blood volume (BV) based on dynamic MRI intensity data after administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium (MMCM) designed for blood pool enhancement. Maps of PS and BV in disease models of adenocarcinoma, intramuscular abscess inflammation, and myocardial reperfusion injury clearly depicted zones of increased permeability (up to approximately 500 microl/cc/h--compared to <25 microl/cc/h in normal tissues). As revealed on PS maps, the rank ordering of studied permeability abnormalities was reperfusion injury > inflammation > tumors. A rapid, automated mapping technique derived from dynamic contrast-enhanced MRI data can be used to facilitate the identification and characterization of pathophysiologic abnormalities, specifically relative increases in blood volume and/or microvascular permeability.

Abscess

Latency of auditory evoked M100 as a function of tone frequency.

This study investigated post-stimulus latency of the M100 component of auditory evoked fields as a function of tone frequency. A 37-channel biomagnetometer was used to record neuromagnetic fields over the temporal lobe in response to monaurally presented tones. M100 peaks in evoked field amplitude were found for each subject. The post-stimulus latency was observed to vary parabolically with tone frequency. Latencies as short as 99 ms were found in response to mid-audio range frequencies (1000-2000 Hz), whereas lower (100-500 Hz) and higher (3000-5000 Hz) frequencies were associated with longer latencies (up to 153 ms). All fields gave M100 dipole localizations in auditory cortex. Although it was not possible to resolve spatial tonotopy, it appears that frequency information is encoded in the temporal evoked response.

Acoustic Stimulation

Sensitivity of high-speed "perfusion-sensitive" magnetic resonance imaging to mild cerebral ischemia.

This study assessed the sensitivity of contrast-enhanced dynamic echo-planar imaging to subtotal stenosis of the middle cerebral artery as a model of mildly compromised cerebral blood supply. Dynamic data was analyzed in terms of the relative cerebral blood volume (rCBV) and bolus peak arrival time (BPAT), and the prognostic utility of these parameters was compared with measurements of the regional apparent diffusion coefficient of water (ADC) with the goal of identifying tissue at risk of future infarct. Dynamic echo-planar MRI in conjunction with bolus administration of a magnetic susceptibility contrast agent was used in a cat model of acute, unilateral cerebral ischemia, induced by partial occlusion (stenosis) of the right middle cerebral artery. The contrast agent transit was analyzed in terms of the regional time of arrival of the peak bolus-induced signal loss as well as the time integral of agent concentration. Pixel-by-pixel maps of cerebrovascular parameters (rCBV, BPAT) were constructed along with spatial maps of the ADC, derived from diffusion-weighted MR images at the same anatomical level. Arterial stenosis was maintained for a 6 h period, after which histological determination of tissue viability was obtained. Maps of BPAT showed sensitivity to mild flow perturbations not detectable from cerebral blood volume estimations from the same bolus injection or from determinations of the apparent diffusion coefficient of water. Of nine animals subjected to subtotal stenosis, BPAT identified compromised tissue in all nine after 1 h of stenosis. No animals had differences in rCBV or ADC at this point. Stenosis was maintained for 6 h in 7 of the cats. After 6 h, two cats had developed identifiable injury on ADC and rCBV maps. Of the remaining five, where rCBV and ADC appeared normal even after 6 h, three exhibited abnormal histological staining, whereas two indeed appeared normal. In the other two cats where initial subtotal stenosis was later made total, the anatomical region identified as "compromised" during stenosis, by the appearance of delayed bolus peak arrival, matched the area of subsequent infarct after total occlusion of the same vessel. Echo planar imaging in conjunction with bolus administration of a magnetic susceptibility contrast agent appears sensitive to mild perturbations to blood supply. These perturbations may not be resolved on synthesized maps of relative cerebral blood volume or apparent diffusion coefficient. Although "compromised" blood supply does not necessarily lead to infarct (over the 6-h course of this study), it may represent tissue particularly at risk of infarct in the event of further insult.

Animals

MRI mapping of microvascular permeability and tissue blood volume.

A quick and automated method for quantitative spatial mapping of tissue characteristics derived from contrast enhanced MR imaging by a macromolecular contrast medium (MMCM) was used in normal rats. Specifically, an established two compartment unidirectional flow kinetic model was automatically implemented on a pixel by pixel basis to calculate permeability surface area product (PS) and tissue fractional blood volume (BV) from MRI dynamic intensity data. The utility of PS and BV maps were evaluated in the normal rat abdomen where a range of fractional BV was found: from 100% in the vena cava to 1% in skeletal muscles, with intermediate values for liver and kidney. Tissue permeability depicted on the PS maps was generally low for normal tissues.

Animals

Comparison of late components in simultaneously recorded event-related electrical potentials and event-related magnetic fields.

We have attempted to define the late components of the event-related magnetic field (ERF) and to relate them to the late components of the event-related electrical potential (ERP). Simultaneous multichannel electroencephalogram (EEG) and magnetoencephalogram (MEG) were recorded in 13 subjects during an auditory oddball paradigm in two series of experiments. EEG responses to frequent tones consisted of the N1 and P2 components of the auditory vertex potential. Responses to rare tones consisted of N1, apparent P2, N2 and P3 components. All EEG components were best seen in the midline and were highly reproducible for all subjects. MEG responses to frequent tones consisted of N1m and P2m components that were highly reproducible only when recorded over the temporal region. By contrast, the ERF to rare tones was less well defined and only the N1m component could be identified satisfactorily. There was little consistent activity in the MEG at the time of occurrence of the N2 and P3 components of the ERP.

Acoustic Stimulation

Noninvasive somatosensory monitoring of the injured inferior alveolar nerve using magnetic source imaging.

PURPOSE: This study evaluates magnetoencephalography (MEG) as an objective monitor for the evaluation of post-traumatic inferior alveolar nerve injuries. MATERIALS AND METHODS: Six patients with unilateral inferior alveolar nerve injuries were assessed using conventional sensory examination techniques. All damaged nerves, and their contralateral controls, were then reexamined using MEG technology. Regions of somatosensory-induced magnetic activity were superimposed on three-dimensional magnetic resonance imaging (MRI) scans to give cortical magnetic source images (MSI). All patients subsequently underwent surgical exploration of the damaged nerves. RESULTS: All six patients had no sensitivity to conventional testing on the damaged side. On evaluation with MEG, all six control nerves had an appropriate cortical signal in response to repetitive lip stimulation. Somatosensory stimulation of two of the six damaged nerves resulted in cortical magnetic field changes. Surgical exploration showed that the four nerves with negative MEG tests had discontinuity defects. In contrast, the two patients with positive MEG signals had intact nerves. CONCLUSION: This technology may differentiate between intact but damaged nerves and transected nerves.

Adult

Task-induced asymmetry of the auditory evoked M100 neuromagnetic field elicited by speech sounds.

The auditory evoked neuromagnetic fields elicited by synthesized speech sounds (consonant-vowel syllables) were recorded in six subjects over the left and right temporal cortices using a 37-channel SQUID-based magnetometer. The latencies and amplitudes of the peaks of the M100 evoked responses were bilaterally symmetric for passively presented stimuli. In contrast, when subjects were asked to discriminate among the same syllabic stimuli, the amplitude of the M100 increased in the left and decreased in the right temporal cortices. Single equivalent current dipole modeling of the activity elicited by all stimulus-types localized to a well-circumscribed area in supratemporal auditory cortex. The results suggest that attentional modulation affects the two supratemporal cortices in a differential manner. Task-conditioned attention to speech sounds is reflected in lateralized supratemporal cortical responses possibly concordant with hemispheric language dominance.

Acoustic Stimulation

Mapping abnormal synovial vascular permeability in temporomandibular joint arthritis in the rabbit using MRI.

An automated method for two-dimensional spatial depiction (mapping) of quantitative physiological tissue characteristics derived from contrast-enhanced MRI was applied to a model of inflammatory disease represented by antigen-induced arthritis of the temporomandibular joint in the rabbit. Specifically, an established two-compartment kinetic model of unidirectional mass transport was implemented on a pixel-by-pixel basis to generate maps of tissue permeability surface area product (PS) and fractional blood volume (BV) based on dynamic MRI intensity data after administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium designed for blood pool enhancement. Maps of PS and BV in a disease model of induced arthritis clearly depicted zones of increased permeability (up to approximately 200 microliters/cc/h-compared to 25 microliters/cc/h in normal tissues).

Animals

Mammary carcinoma model: correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density.

PURPOSE: To determine the relationship between capillary density, a recognized surrogate of tumor angiogenesis, and magnetic resonance (MR) imaging-derived estimates of plasma volume (PV) and microvascular permeability in two mammary carcinoma models. MATERIALS AND METHODS: Dynamic spin-echo imaging was performed by using albumin-(gadolinium-diethylenetriaminepentaacetic acid)34, a prototype blood-pool contrast medium, in 14 rats with a subcutaneously implanted slow- or fast-growing subtype of R3230 mammary carcinoma. Data were fitted to an established two-compartment kinetic model to estimate PV and permeability. RESULTS: MR imaging-derived tumor PVs and permeabilities increased exponentially with increasing capillary density. MR imaging-derived microvascular characteristics correlated strongly with histologic capillary density, with an r2 of .85. CONCLUSION: Contrast medium-enhanced MR imaging may prove useful in estimating angiogenic activity in carcinomas. MR imaging may be superior to histologic assay because it is noninvasive, can be used to "sample" the entire tumor, and reflects both anatomic and physiologic characteristics.

Albumins

Contrast-enhanced MR imaging assessment of tumor capillary permeability: effect of irradiation on delivery of chemotherapy.

PURPOSE: To assess the effect of x rays on tumor capillary permeability with macromolecular contrast medium (MMCM)-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: One of paired R3230 mammary adenocarcinomas implanted in the flanks of 48 Fischer rats was treated with a single 5- or 15-Gy dose of x rays. After 1 or 3 days, MR imaging in 30 rats was performed unenhanced and enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid)30 (0.02 mmol gadolinium per kilogram body weight). Signal intensity enhancement was analyzed to estimate fractional blood volume and permeability-surface area product (PS). In 18 irradiated rats, 2.5 mg/kg cisplatin was injected intravenously, and fractional tumor platinum concentrations were measured spectrometrically. RESULTS: MR imaging showed highest capillary permeability 1 day after 15 Gy (PS 110% above control [P<.001]); PS was elevated 57% 1 day after 5 Gy and 63% 3 days after 15 Gy (P<.05). The largest mean tumor platinum fraction occurred 1 day after 15 Gy: 48% versus 20% (control)(P<.05). CONCLUSION: Transient irradiation-induced increase in tumor capillary permeability to cisplatin can be quantified with MMCM-enhanced MR imaging.

Albumins

Early detection of acute tubular injury with diffusion-weighted magnetic resonance imaging in a rat model of myohemoglobinuric acute renal failure.

We evaluated the feasibility of magnetic resonance imaging (MRI) for early detection of tubular injury by monitoring changes in the apparent diffusion coefficient (ADC) of renal water in a rat model of myohemoglobinuric glycerol-induced acute renal failure (ARF). Diffusion-weighted MRI was performed concurrently with measurements of serum creatinine and blood urea nitrogen (BUN), evaluation of renal perfusion with dynamic contrast-enhanced MRI, and renal morphological examination. ADC values in the cortex and outer medulla significantly declined within minutes after the glycerol administration (70-75% of control at 4 min and 50-60% of control at 15 min). Contrast-enhanced MRI demonstrated renal hypoperfusion at 20 min after the onset of injury. Light microscopy showed normal glomeruli and edematous tubular epithelial cells at 10 and 30 min, with more severe swelling and protein casts at 30 min. No changes in serum creatinine or BUN levels were detected. We hypothesize that decrease in renal ADC may be attributed to renal ischemia and to subsequent intracellular accumulation of diffusion-restricted water. Similar imaging evaluation in other experimental models of ARF, and in patients, will define the diagnostic value of renal ADC changes in early detection of acute tubular injury.

Acute Kidney Injury

Evaluation of recombinant human basic fibroblast growth factor (rhbFGF) as a cerebroprotective agent using high speed MR imaging.

The potential cerebroprotective effects of recombinant human basic fibroblast growth factor (rhbFGF) were evaluated in a feline model of acute cerebral ischemia using high-speed magnetic resonance imaging (MRI) in conjunction with immunohistology. The neuroprotective efficacy of three doses of rhbFGF was evaluated in a unilateral middle cerebral artery (MCA) occlusion/reperfusion model. Ten h following a 2 h period of MCA occlusion in control (vehicle-treated) animals, cerebral perfusion in the ischemic hemisphere was 58 +/- 17% of the contralateral normal hemisphere. Corresponding ischemic/normal perfusion ratios in rhbFGF-treated groups were not significantly different: 54 +/- 16% (14 micrograms/kg/h dose), 40 +/- 19% (42 micrograms/kg/h dose) and 75 +/- 8% (125 micrograms/kg/h dose). Triphenyltetrazolium chloride histopathological assessment demonstrated brain damage in vehicle-treated animals comprising 31 +/- 15% of the hemisphere; in rhbFGF-treated groups injury was not significantly different: 19 +/- 4% (14 micrograms/kg/h rhbFGF), 24 +/- 6% (42 micrograms/kg/h rhbFGF) and 16 +/- 10% (125 micrograms/kg/h rhbFGF). Immunohistochemical analysis of brain sections using glial fibrillary acidic protein (GFAP) revealed that in animals that showed marked perfusion deficits throughout the entire experiment (regardless of treatment), GFAP staining was elevated contralateral to the occlusion and absent ipsilaterally. While some tendency towards protection is found, particularly at higher doses of rhbFGF, it must be concluded that in the chosen stroke model and time interval, the doses used did not significantly improve reperfusion or confer significant cerebroprotective benefit. Non-invasive high-speed MRI was found to be useful for evaluation of putative cerebroprotective agents.

Animals

Quantification of liver blood volume: comparison of ultra short TI inversion recovery echo planar imaging (ULSTIR-EPI), with dynamic 3D-gradient recalled echo imaging.

An ultra-short TI inversion recovery echo-planar imaging (ULSTIR-EPI) sequence was designed to reduce the influence of water exchange on fractional tissue blood volume (BV) estimation by measurement of T1-changes induced by a gadolinium-based macromolecular contrast medium (MMCM). Fractional liver BV in rats, estimated by ULSTIR-EPI was compared for accuracy to a fast T1-weighted three-dimensional gradient-echo (3D-SPGR, 3D-spoiled gradient recalled acquisition in a steady state) sequence using an in vitro inductively coupled plasma atomic emission spectroscopy (ICP-AES) assay for BV as a standard. Liver images for fractional BV estimation were acquired in eight rats using both ULSTIR-EPI and 3D-SPGR before and after (within 3 to 12 min) intravenous bolus administration of albumin-Gd-DTPA30 (0.05 mmol Gd/kg). Whereas both MR techniques may be useful for fractional tissue BV estimation, ULSTIR-EPI offers certain advantages including greater accuracy, direct T1 maps, and minimization of transendothelial proton exchange effects. 3D-SPGR imaging offers better spatial resolution, current availability on standard clinical MR systems, and acceptable accuracy.

Albumins