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Biomedical subjects

Guangping Dai

Publications and source records attributed to Guangping Dai.

8 recordsLinked to original sources

Remifentanil administration reveals biphasic phMRI temporal responses in rat consistent with dynamic receptor regulation.

Many pharmacological stimuli influence multiple neurotransmitter systems in the brain, and the dynamics of the functional brain response can vary regionally. In this study, the temporal response of cerebral blood volume (CBV) was employed to spatially segment cerebral effects due to infusion of a potent mu-opioid receptor agonist. Repeated intravenous injection of 10 mug/kg remifentanil in rats caused reproducible regional positive, negative, and biphasic changes in CBV. Three temporal processes were identified in the cerebral response and analyzed within the framework of the general linear model. Firstly, a slow component identified CBV changes that were almost exclusively negative, and the spatial distribution was similar to the inhibition produced by morphine (200 microg/kg). The largest CBV reductions occurred in caudate, accumbens, ventral hippocampus, cingulate, and piriform cortex. Secondly, a more rapid temporal component corresponded primarily with a regional distribution of positive changes in CBV consistent with GABAergic inhibition of hippocampal interneurons and associated projections. Thirdly, a response with the dynamics of mean arterial blood pressure correlated positively with CBV changes in hypothalamus, consistent with a central mechanism for control of blood pressure. We propose that the dominant source of the temporal variance in signal is dynamic modulation of drug targets by receptor endocytosis, an established effect in vitro. These results suggest that the temporal response of fMRI signal reflects underlying neurobiological processes, so that temporal decomposition strategies may aid interpretation of pharmacological mechanisms by identifying interconnected regions or those associated with common neural targets and processes.

Action Potentials↗

In vivo imaging of tumor response to therapy using a dual-modality imaging strategy.

In vivo assessment of the outcome of cancer therapy is hampered by the paucity of imaging probes that target tumors specifically and noninvasively. The importance of such probes increases with the continuous development of chemotherapeutics and the necessity to evaluate their effectiveness in a clinical setting. We have recently reported on a dual-modality imaging probe specifically targeting the underglycosylated mucin-1 tumor-specific antigen (uMUC-1), which is one of the early hallmarks of tumorigenesis in a wide variety of tumors. This probe consists of crosslinked superparamagnetic iron oxide nanoparticles (CLIO) for MR imaging, modified with Cy5.5 dye (for near infrared optical fluorescence imaging (NIRF)), and has peptides (EPPT), specifically recognizing uMUC-1, attached to the nanoparticle's dextran coat. In the present study, we demonstrated that this probe could not only detect orthotopically implanted preclinical models of adenocarcinomas but could also track tumor response to chemotherapy in vivo in real time. Considering the high cost associated with the development and testing of new cancer therapeutics and the need for accurate, noninvasive assessment of their effectiveness, we believe that the developed probe represents a valuable research tool relevant to clinical discovery.

Adenocarcinoma↗

In vivo imaging of islet transplantation.

Type 1 diabetes mellitus is characterized by the selective destruction of insulin-producing beta cells, which leads to a deficiency in insulin secretion and, as a result, to hyperglycemia. At present, transplantation of pancreatic islets is an emerging and promising clinical modality, which can render individuals with type 1 diabetes insulin independent without increasing the incidence of hypoglycemic events. To monitor transplantation efficiency and graft survival, reliable noninvasive imaging methods are needed. If such methods were introduced into the clinic, essential information could be obtained repeatedly and noninvasively. Here we report on the in vivo detection of transplanted human pancreatic islets using magnetic resonance imaging (MRI) that allowed noninvasive monitoring of islet grafts in diabetic mice in real time. We anticipate that the information obtained in this study would ultimately result in the ability to detect and monitor islet engraftment in humans, which would greatly aid the clinical management of this disease.

Animals↗

Tissue edema does not change gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced T1 relaxation times of viable myocardium.

PURPOSE: To determine whether tissue edema changes gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced T1 relaxation times of the viable myocardium. MATERIALS AND METHODS: A total of 16 isolated pig hearts were divided into four groups (N=4/group) and perfused in a Langendorff apparatus. Gd-DTPA was injected into the aortic perfusion line. Tissue edema was then induced by two hours of simultaneous arterial/venous perfusion (SAVP). Myocardial water content and T1 relaxation times were monitored throughout SAVP. The volumes of the extracellular and intracellular compartments were assessed using 31P MRS-detectable markers, phenylphosphonic acid (PPA) and dimethyl methylphosphonate (DMMP). RESULTS: Tissue water content in both viable and infarcted myocardium increased significantly during two-hour SAVP. However, Gd-DTPA-enhanced T1 relaxation times of the viable myocardium remained relatively unchanged. Infarcted myocardium, on the other hand, exhibited significant T1 shortening during SAVP. Furthermore, SAVP resulted in significant expansions of both extracellular and intracellular compartments, but the ratio of the volumes of the two compartments remained relatively constant. CONCLUSION: Tissue edema in the viable myocardium does not increase the relative distribution volume of the contrast agent. As a result, edema does not change Gd-DTPA-enhanced T1 relaxation times of the viable myocardium.

Analysis of Variance↗

In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe.

One of the most difficult challenges of oncology is to improve methods for early tumor detection, which is crucial for the success of cancer therapy and greatly improves the survival rate. Underglycosylated mucin-1 antigen (uMUC-1) is one of the early hallmarks of tumorigenesis and is overexpressed and underglycosylated on almost all human epithelial cell adenocarcinomas as well as in nonepithelial cancer cell lines, as well as in hematological malignancies such as multiple myeloma, and some B-cell non-Hodgkin lymphomas. In this study, we designed, synthesized, and tested a novel multimodal imaging probe specifically recognizing in vivo uMUC-1 antigen in an animal model of human cancer. Furthermore, in vivo magnetic resonance- and near-infrared-imaging experiments on tumor-bearing animals showed specific accumulation of the probe in uMUC-1-positive tumors and virtually no signal in control tumors. We expect that this probe has a potential to greatly aid in screening prospective patients for early cancer detection and in monitoring the efficacy of drug therapy.

Amino Acid Sequence↗

Mapping myocardial viability using interleaved T1-T2* weighted imaging.

The present study was to evaluate the efficacy of our interleaved T1-T2* weighted imaging for assessing myocardial viability. The left anterior descending coronary artery (LAD) of pig hearts (n = 7) were occluded for 2 h, followed by 1 h reperfusion. After removed from animals, the hearts were perfused in a Langendorff apparatus with a mixture of pig blood and crystalloid solution in 1:1 ratio. T1 relaxation times of the myocardium were measured with a TurboFLASH inversion-recovery sequence. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.05 mmol/kg body wt) was then injected as a bolus into the aortic perfusion line. The first pass of the contrast agent through the heart was followed using the interleaved T1-T2* imaging sequence. Once the concentration of the contrast agent was in an equilibrium state, T1 relaxation times were measured again. It was found that the percentage recovery of T2* intensity (PRT2*) at the maximum T1 intensity measured during the first pass of the contrast agent with the interleaved T1-T2* imaging was significantly higher in infarcted myocardium than in normal myocardium. Moreover, the regions showing a high T2* percentage recovery on PRT2* maps matched well with the infarcted myocardium demarcated with triphenyl tetrazolium chloride (TTC) staining. We therefore conclude that infarcted myocardium can be delineated using the interleaved T1-T2* imaging method.

Animals↗

Retrograde cardioplegia.

OBJECTIVE: This study was undertaken to compare the efficacy of retrograde cardioplegia for myocardial perfusion with that of antegrade cardioplegia at the same flow rate. METHODS: Colored microspheres were used in rat hearts to assess the capillary flow of cardioplegia solution. Myocardial perfusion was evaluated with magnetic resonance imaging in pig hearts. Phosphorus 31 magnetic resonance spectroscopy was used to determine the efficacies of the cardioplegic techniques in sustaining myocardial energy metabolism. RESULTS: At the same flow rate, the number of colored microspheres delivered to the capillaries by retrograde cardioplegia (15 +/- 1 microspheres/mm2) was significantly lower than that delivered by antegrade cardioplegia (29 +/- 2 microspheres/mm2). Furthermore, only 19% +/- 3% of the colored microspheres delivered to the capillaries by retrograde cardioplegia were found in the arteriolar portions of the capillaries, whereas most (80% +/- 3%) remained in the venular portions. Moreover, magnetic resonance images showed that contrast-enhanced signal-time courses obtained from different regions of the myocardium during retrograde cardioplegia varied significantly. Localized phosphorus 31 spectra showed that retrograde cardioplegia required a higher flow rate than did antegrade cardioplegia to sustain normal myocardial energy metabolism. CONCLUSIONS: We conclude that retrograde cardioplegia provides significantly less capillary flow than does antegrade cardioplegia. Its microvascular perfusion varies significantly among the various small areas of the myocardium. As a result, its efficacy in sustaining normal myocardial energy metabolism is lower than that of antegrade cardioplegia.

Animals↗

Simultaneously monitoring both T(1) and T(2)* signal intensities on a bolus injection of Gd-DTPA may distinguish infarcted myocardium.

PURPOSE: To determine whether injured myocardium may be identified by simultaneously monitoring contrast-induced T(1) and T(2)* signal intensity time-course changes with an interleaved T(1)-T(2)* imaging sequence. MATERIALS AND METHODS: Gadolinium-diethylene triamine pentaacetic acid (0.05 mmol/ kg) was injected as a bolus into ex vivo pig hearts, and simultaneous T(1) and T(2)* time-courses were obtained during the first pass. RESULTS: Observing contrast-enhanced R(1) or R(2)* rates (1/T(1) or 1/T(2)* times, respectively) early after contrast injection did not fully differentiate viable from nonviable myocardium. T(2)* recovery at maximal T(1) signal intensity, measured using simultaneous T(1) and T(2)* imaging, displayed a significantly different percentage recovery (P < 0.05) among normal (30.5 +/- 2.4% of baseline value), reperfused infarcted (63 +/- 7.2%), and low-reflow infarcted (90 +/- 2.8%) myocardium. CONCLUSION: Simultaneously monitoring both T(1) and T(2)* signal intensities may help in the assessment of myocardial injury.

Analysis of Variance↗