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T Reese

Publications and source records attributed to T Reese.

At least 19 recordsLinked to original sources
PubMed2004

Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration.

The mechanisms underlying the signal changes observed with pharmacological magnetic resonance imaging (phMRI) remain to be fully elucidated. In this study, we obtained microdialysis samples in situ at 5-min intervals during phMRI experiments using a blood pool contrast agent to correlate relative cerebral blood volume (rCBV) changes with changes in dopamine and cocaine concentrations following acute cocaine challenge (0.5 mg/kg iv) in the rat over a duration of 30 min. Three brain areas were investigated: the dorsal striatum (n = 8), the medial prefrontal cortex (mPFC; n = 5), and the primary motor cortex (n = 8). In the striatum and mPFC groups, cocaine and dopamine temporal profiles were tightly correlated, peaking during the first 5-min period postinjection, then rapidly decreasing. However, the local rCBV changes were uncorrelated and exhibited broader temporal profiles than those of cocaine and dopamine, attaining maximal response 5-10 min later. This demonstrates that direct vasoactivity of dopamine is not the dominant component of the hemodynamic response in these regions. In the motor cortex group, microdialysis revealed no local change in dopamine in any of the animals, despite large local cocaine increase and strong rCBV response, indicating that the central hemodynamic response following acute iv cocaine challenge is not driven directly by local dopamine changes in the motor cortex. The combination of phMRI and in situ microdialysis promises to be of great value in elucidating the relationship between the phMRI response to psychoactive drugs and underlying neurochemical changes.

Animals↗
PubMed2001

Functional recovery after brain lesion--contralateral neuromodulation: an fMRI study.

Behavioral recovery takes place even after permanent damage to the entire brain region normally controlling sensorimotor hind limb function in the rat. In our study, 2 weeks after full behavioral recovery from an experimental unilateral permanent brain damage, the topographic representation of the previous paretic hindlimb was investigated by fMRI. The analysis showed that during electrical stimulation of the previously paretic hindlimb, two normally inactive brain regions were now being activated. One region was the non-damaged contralateral sensori-motor cortex and the other region was located lateral to the lesion. These results suggest that behavioral recovery can be explained by functional reorganization and neuromodulation of the brain.

Afferent Pathways↗
PubMed2000

Regional brain activation by bicuculline visualized by functional magnetic resonance imaging. Time-resolved assessment of bicuculline-induced changes in local cerebral blood volume using an intravascular contrast agent.

Functional magnetic resonance imaging (fMRI) has been applied to study rat focal brain activation induced by intravenous administration of the GABA(A) antagonist bicuculline. Using magnetite nanoparticles as a blood pool contrast agent, local changes in cerebral blood volume (CBV) were assessed with high temporal (10 s) and spatial (0.35 x 0.6 mm(2)) resolutions. Upon infusion of the bicuculline region-specific increases in CBV have been observed, suggesting CBV to reflect brain activity. During the first 2 min, the signal increases were predominant in the cortex, followed by increases in other brain areas, such as the caudate putamen, thalamus and cerebellum. Ten minutes after the start of infusion, a dominant response was observed in the thalamus, while in the caudate putamen a biphasic response pattern was seen. The magnitude of the signal responses in all brain regions was dependent on the dose of bicuculline and, in general, matched the known distribution of GABA(A) binding sites. This study suggests that pharmacological fMRI, displaying brain function at the highly specific level of drug-receptor interaction, should foster our understanding of normal and pathological brain function.

Animals↗
PubMed2000

Cytoprotection does not preserve brain functionality in rats during the acute post-stroke phase despite evidence of non-infarction provided by MRI.

In animal models of stroke the promise of a therapy is commonly judged from infarct size measurements, assuming that a reduction in infarct size results in reduction of the functional deficits. We have evaluated the validity of the concept that structural integrity translates into functional integrity during the acute post-stroke period (24 h). Unilateral permanent middle cerebral artery occlusion (pMCAO) in Fischer F344 rats leads to infarcts comprising the ipsilateral striatum and cortical structures, including the somatosensory cortex. Infarct volumes were assessed using magnetic resonance imaging (MRI) methods (T(2), diffusion, perfusion MRI). The functional integrity of the somatosensory cortex was assessed by functional MRI (fMRI) measuring changes in local cerebral blood volume, and by assessing the forelimb grip strength and the beam-walking performance of the animals. Treatment with the calcium antagonist isradipine (2.5 mg/kg injected s.c. immediately after pMCAO) reduced the total infarct size by more than 40% compared to vehicle-injected controls. In particular, the ipsilateral somatosensory cortex appeared normal in diffusion- and T(2)-weighted MRI images. In sham-operated rats simultaneous electrical stimulation of both forepaws led to similar activation of both somatosensory cortices, while in pMCAO animals given vehicle only the contralateral cortex showed an fMRI response. Similarly, in pMCAO rats treated with isradipine, functional activation following bilateral electrical stimulation was only detected in the contralateral somatosensory cortex despite the normal appearance of the ipsilateral cortex in MRI images. Furthermore, fMRI responses to pharmacological stimulation with bicuculline were virtually absent in the ipsilateral somatosensory cortices both in vehicle- and isradipine-treated rats. Finally there was no significant difference between vehicle- and isradipine-treated animals upon the performance of beam-walking test or in forelimb grip strength. It is concluded that during the acute (24 h) post-occlusion period, structural integrity in the somatosensory cortex revealed by MRI does not translate into preservation of function.

Adenosine Triphosphate↗
PubMed2000

Intermittent use of amifostine during postoperative radiochemotherapy and acute toxicity in rectal cancer patients.

PURPOSE: Amifostine has been shown to be able to reduce acute radiation toxicity if administered daily prior to radiation during a course of a conventionally fractionated radiotherapy. A disadvantage is the necessity of daily intravenous injection. We have used amifostin in patients undergoing adjuvant radiochemotherapy for rectal cancer. Amifostine was administered only in the first and fifth week of radiotherapy together with 5-FU chemotherapy. The objective was to determine whether the intermittent use of amifostine may be effective in reducing acute radiation toxicity. PATIENTS AND METHODS: From September 1997 through October 1998, 30 patients with stage II/III rectal cancer underwent postoperative radiochemotherapy at our department. All patients had undergone curative (R0) resection and received 50.4 Gy to the pelvis with a 3-field technique using a belly board followed by a boost of 5.4 Gy to the presacral space in conventional fractionation with 1.8 Gy per fraction. 5-FU chemotherapy was administered as 120-hours continuous infusion in the first and fifth radiation week via a central venous catheter in a daily dosage of 1,000 mg/m2. All patients were offered to participate in a phase-II study using additional amifostine. Fifteen patients participated and received 500 mg amifostine daily on chemotherapy days (days 1 to 5 and 29 to 33) immediately prior to the daily radiation fraction. Fifteen patients did not participate and served as non-randomized control. The study was approved by the ethical committee of the Martin-Luther-University and informed consent was obtained from all patients. RESULTS: The distribution of patients' characteristics and prognostic parameters was comparable in both groups. Side effects of amifostine were mild and included hypotension (53% grade I, 7% grade II) and nausea (47% grade I, 13% grade II). Antiemetics were not routinely used. All patients completed radiochemotherapy plus amifostine without unplanned breaks or dose reductions. One patient developed a cerebral infarction which was considered to be not related to the use of amifostine. As compared to the non-randomized control group, patients with additional amifostine had less acute skin and bowel toxicity (maximum erythema score 1.47 +/- 0.64 without vs 0.87 +/- 0.52 with amifostine, p = 0.009 and maximum diarrhea score 1.07 +/- 1.03 vs 0.40 +/- 0.63, p = 0.044). Oral 5-FU-related mucositis and hematological toxicity were not significantly different. CONCLUSIONS: In this phase-II study, amifostine significantly reduced acute skin and bowel toxicity of adjuvant chemoradiation in patients with rectal cancer even if the drug was administered only intermittently and not during the whole course of radiotherapy. This finding might be important with regard to intense combined regimes and should be further investigated.

Amifostine↗
PubMed2000

Immunohistochemical determination of HER-2/neu expression in invasive breast carcinoma.

Numerous methods exist for HER-2/neu assessment; however, technical and interpretive standardization is virtually absent. We evaluated 2 commercially available antibodies on routinely fixed paraffin-embedded tissue sections to establish our own guidelines. Thirty-three cases of infiltrating breast carcinoma were evaluated simultaneously with monoclonal and polyclonal antibodies. Only membranous staining, no matter how focal, was considered positive. An additional 32 tumors were studied subsequently using only the polyclonal antibody. Of all carcinomas, 13.0% showed immunohistochemical evidence of HER-2/neu overexpression. High-grade tumors were more often positive. There was no HER-2/neu gene expression in the benign epithelium that generally was present in the tissue section or in any of the well-differentiated tumors tested. The polyclonal antibody proved more sensitive than the monoclonal antibody. While true cytoplasmic staining was present occasionally, it did not create substantial difficulty in interpretation. The polyclonal antibody cost substantially less than the monoclonal antibody. Fluorescence in situ hybridization assay for HER-2/neu gene amplification performed on 32 of 65 cases showed concordant results in 31 cases. The immunohistochemical assay for HER-2/neu gene overexpression, using our methods, is accurate, economic, and easily integrated into the laboratory.

Antibodies↗
PubMed1999

In vivo magnetic resonance methods in pharmaceutical research: current status and perspectives.

In the last decade, in vivo MR methods have become established tools in the drug discovery and development process. In this review, several successful and potential applications of MRI and MRS in stroke, rheumatoid and osteo-arthritis, oncology and cardiovascular disorders are dealt with in detail. The versatility of the MR approach, allowing the study of various pathophysiological aspects in these disorders, is emphasized. New indication areas, for the characterization of which MR methods have hardly been used up to now, such as respiratory, gastro-intestinal and skin diseases, are outlined in a subsequent section. A strength of MRI, being a non-invasive imaging modality, is the ability to provide functional, i.e. physiological, readouts. Functional MRI examples discussed are the analysis of heart wall motion, perfusion MRI, tracer uptake and clearance studies, and neuronal activation studies. Functional information may also be derived from experiments using target-specific contrast agents, which will become important tools in future MRI applications. Finally the role of MRI and MRS for characterization of transgenic and knock-out animals, which have become a key technology in modern pharmaceutical research, is discussed. The advantages of MRI and MRS are versatility, allowing a comprehensive characterization of a diseased state and of the drug intervention, and non-invasiveness, which is of relevance from a statistical, economical and animal welfare point of view. Successful applications in drug discovery exploit one or several of these aspects. In addition, the link between preclinical and clinical studies makes in vivo MR methods highly attractive methods for pharmaceutical research.

Animals↗
PubMed1999

Magnetic resonance angiography of the rat cerebrovascular system without the use of contrast agents.

We describe and discuss the application of three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) to visualize non-invasively the cerebral vasculature of the rat. MR angiograms of healthy spontaneously hypertensive rats were obtained without the use of contrast agents. Total imaging time ranged from 1 to 50 min for a 3D data set. The influences of the data matrix and the inflow delay on the image quality and the total imaging time are assessed and discussed. Varying the inflow delay yielded in addition semiquantitative information on hemodynamics. The method was applied to obtain angiograms in rat models of permanent and temporal middle cerebral artery occlusion. Occlusion and reopening of the vessel could easily be verified by MRA. However, after reperfusion a slight reduction in blood flow was observed.

Animals↗
PubMed1998

In situ measurements of creatine kinase flux by NMR. The lessons from bioengineered mice.

P-31 nuclear magnetic resonance (NMR) is uniquely suited to measure the kinetics of the phosphoryl-exchange reaction catalyzed by creatine kinase in intact mammalian tissue, especially striated muscle. Recently developed transgenic mouse models of the creatine kinase iso-enzyme system open novel opportunities to assess the functional importance of the individual iso-enzymes and their relative contribution to the total in situ flux through the CK reaction. This chapter reviews the most recent findings from NMR flux measurements on such genetic models of CK function. Findings in intact mouse skeletal and cardiac muscle in vivo are compared to data from purified mitochondrial and cytosolic creatine kinase in vitro. The relevance of findings in transgenic animals for the function of CK in wild-type tissue is described and the perspectives of transgenic techniques in future quantitative studies on the creatine kinase iso-enzyme system are indicated.

Animals↗
PubMed1997

Fluxes through cytosolic and mitochondrial creatine kinase, measured by P-31 NMR.

The kinetic properties of the cytoplasmic and the mitochondrial iso-enzymes of creatine kinase from striated muscle were studied in vitro and in vivo. The creatine kinase (CK) iso-enzyme family has a multi-faceted role in cellular energy metabolism and is characterized by a complex pattern of tissue-specific expression and subcellular distribution. In mammalian tissues, there is always co-expression of at least two different CK isoforms. As a result, previous studies into the role of CK in energy metabolism have not been able to directly differentiate between the individual CK species. Here, we describe experiments which were directed at achieving this goal. First, we studied the kinetic properties of the muscle-specific cytoplasmic and mitochondrial CK isoforms in purified form under in vitro conditions, using a combination of P-31 NMR and spectrophotometry. Secondly, P-31 NMR measurements of the flux through the CK reaction were carried out on intact skeletal and heart muscle from wild-type mice and from transgenic mice, homozygous for a complete deficiency of the muscle-type cytoplasmic CK isoform. Skeletal muscle and heart were compared because they differ strongly in the relative abundance of the CK isoforms. The present data indicate that the kinetic properties of cytoplasmic and mitochondrial CK are substantially different, both in vitro and in vivo. This finding particularly has implications for the interpretation of in vivo studies with P-31 NMR.

Animals↗
PubMed1996

Dynamic changes in water ADC, energy metabolism, extracellular space volume, and tortuosity in neonatal rat brain during global ischemia.

To obtain a better understanding of the mechanisms underlying early changes in the brain water apparent diffusion coefficient (ADC) observed in cerebral ischemia, dynamic changes in the ADC of water and in the energy status were measured at postnatal day 8 or 9 in neonatal rat brains after cardiac arrest using 1H MRS/MRI and 31P MRS, respectively. The time courses of the MR parameters were compared with changes in the extracellular space (ECS) volume fraction (alpha) and tortuosity (lambda), determined from concentration-time profiles of tetramethylammonium applied by iontophoresis. The data show a decrease of the ADC of tissue water after induction of global ischemia of which the time course strongly correlates with the time course of the decrease in the ECS volume fraction and the increase in ECS tortuosity. This indicates that cell swelling is an important cause for the ADC decrease of water.

Animals↗
PubMed1995

A fast method for in vivo lactate imaging.

A robust method for fast lactate imaging is presented using a combination of a lactate editing sequence and a one-shot imaging experiment. The lactate editing method is based on manipulation of the phase of the lactate CH3 signal via J-modulation. This is applied as a preparation experiment to the U-FLARE imaging sequence. Phantom experiments are presented in which the quality of water and lipid suppression is established. Edited lactate images with a spatial resolution of 3 microL and total measuring time of 15.8 min are shown. These were obtained from a hemispherical ischemia in the gerbil brain. The images are compared with diffusion-weighted water images.

Animals↗
PubMed1992

On the application of ultra-fast RARE experiments.

The ultra-fast application of the RARE experiment is described in detail, with special emphasis on its multifarious applications with preparation experiments that produce transverse magnetization. The factors affecting the temporal evolution of the magnetization during the experiment are described, and the implications for the slice profile when using a Gaussian refocusing pulse are experimentally examined. The choice of phase-encoding scheme for use with preparation experiments is discussed, as is the use of various phase-encoding schemes to reduce line broadening in the phase-encoding direction if a number of averages are acquired. An explanation for the decomposition of the echo are into two components if the read gradient is imbalanced is given, and the experimental conditions necessary for the coherent addition of these two echo groups are described. An alternative sequence that removes one of these groups from the acquisition window is proposed. The sensitivity of the sequence to flow and motion is investigated, and the drastic loss of signal in this situation explained. The in vivo and in vitro application of preparation experiments leading to the accurate measurement of T1, T2, diffusion constant, and magnetization transfer characteristics is presented. The implementation of zoom-imaging using spin- and stimulated-echo preparation is described, and 3D in vivo spin-echo zoom images are presented. Simple phantom experiments demonstrating the feasibility of chemical-shift selective and spectroscopic imaging are also given.

Animals↗
PubMed1988

Correlation of minimum coronary lumen diameter with left ventricular functional impairment induced by atrial pacing.

To understand whether quantitative measurement of minimal coronary luminal diameter is a better method than percent diameter narrowing for assessing the functional impairment of myocardial contractility produced by coronary artery stenoses, measurements were made from 37 stenotic segments in 27 patients with coronary artery disease and from corresponding segments in 10 subjects without coronary artery narrowing. An assessment of the reliability of the 2 types of measurements was made by correlating them with the physiologic parameters of both segmental wall motion and global ejection fraction response induced by atrial pacing. Digitally acquired coronary angiograms were used to facilitate quantitative analysis. Measurements by edge detection and videodensitometry correlated closely (r = 0.94). Percent diameter narrowing correlated moderately with the change in ejection fraction (r = -0.41) or with the change in segmental wall motion (r = -0.44). The measurement of minimal lumen diameter correlated with the change in global ejection fraction (r = 0.61) and did so even better with the change in segmental wall motion (r = 0.78, p less than 0.05). A minimal lumen diameter of less than or equal to 1.5 mm identified patients likely to have a functional impairment during atrial pacing as assessed by either global ejection fraction or segmental wall motion defects. We conclude that minimal coronary luminal diameter provides a better method than percent diameter narrowing calculations to measure the anatomic severity of coronary artery narrowing.

Angiography↗
PubMed1987

Videodensitometric determination of minimum coronary artery luminal diameter before and after angioplasty.

Quantitative measurements of coronary stenoses were made from digital coronary angiograms in 19 patients before and after percutaneous transluminal coronary angioplasty (PTCA). Two methods of measurement were compared. Mean stenosis before PTCA was 67 +/- 10% by the edge detection method and 67 +/- 12% by videodensitometry (difference not significant). After PTCA, the mean stenosis was 32 +/- 14% by edge detection and 30 +/- 13% by videodensitometry (difference not significant). In addition, a new method was developed to rapidly calculate the absolute minimum luminal area and diameter by videodensitometry. The minimum luminal diameter before PTCA was 1.0 +/- 0.5 mm and after PTCA increased to 2.4 +/- 0.5 mm (p less than 0.001). The validity of the videodensitometric method was analyzed in a series of Lucite phantom studies, which suggested that when there is an irregular angiographic appearance, the densitometric method may be more accurate than standard edge detection methods. Digital acquisition of coronary angiograms provides a means for rapid application of quantitative analysis during coronary interventional procedures.

Angioplasty, Balloon↗