抗棘球蚴药物研究:3-取代苯基-5-取代-1,2,4-噁二唑的合成

合成了3-取代苯基-5-取代-1,2,4-(口恶)二唑类化合物50个,经感染棘球蚴的小鼠初筛,部分化合物对棘球蚴有不同程度的作用,化合物13、28和30对棘球蚴的囊重抑制率分别为70、75.6和71.6%,其中化合物13对棘球蚴的生发层有损害作用。     

MRI gadolinium enhancement of bone marrow: age-related changes in normals and in diffuse neoplastic infiltration

 Objective: To quantify gadolinium-related enhancement in the bone marrow of the spine in normals and in patients with homogeneous diffuse malignant bone marrow infiltration. Design and patients: The patients consisted of two groups: group 1 comprised 94 healthy adults (18–86 years) without bone marrow disease and group 2 comprised 30 patients with homogeneous diffuse malignant bone marrow infiltration due to myeloma (n=20) or breast carcinoma (n=10). All patients received intravenous gadopentetate dimeglumine (Gd-DTPA), 0.1 mmol/kg body weight. Pre- and postcontrast signal intensity (SI) on T1-weighted spin-echo (SE) images (TR/TE: 572 ms/15 ms) was measured over a region of interest (ROI) and the percentage SI increase was calculated. The results were confirmed by bone marrow biopsy (n=20) and clinical parameters (n=10). Dynamic contrast-enhanced studies using a spoiled gradient-recalled-echo (GRE) sequence (TR/TE/α: 68 ms/6 ms 75°) were performed in 10 controls with normal bone marrow. Results and conclusion: Contrast material enhancement in healthy persons can vary greatly (range 3–59%, mean 21%, SD 11%). With increasing age there is a significant decrease in contrast enhancement (Pearson’s correlation, P<0.01). The percentage SI increase in patients with intermediate-grade (biopsy 20–50 vol%) and high-grade (biopsy >50 vol%) diffuse malignant bone marrow infiltration was significantly higher than in normals (mean 67%, SD 34%, P<0.001). Low-grade (biopsy <20 vol%) diffuse malignant bone marrow infiltration can not be assessed by non-enhanced T1-weighted SE images or Gd-DTPA application. In conclusion, contrast material enhancement in healthy persons can vary greatly and is dependent on age, while intermediate-grade and high-grade diffuse malignant bone marrow infiltration can be objectively assessed with SI measurements.     

Gadoteridol dose dependence in MR imaging of a liver abscess model

A necrotic liver abscess model was studied with magnetic resonance (MR) imaging at 1.5 T before and after intravenous administration of gadoteridol at doses of 0.1, 0.25, and 0.5 mmol/kg in 24 rabbits. Enhancement characteristics and lesion delineation were assessed with both breath-hold and non-breath-hold imaging techniques. Lesion delineation, as assessed both by signal intensity measurements and evaluations by two image readers blinded to imaging technique, was greatest on high-dose (0.5 mmol/kg) breath-hold images. Lesion rim enhancement was seen consistently only on postcontrast images obtained at a dose of 0.5 mmol/kg and progressed with time after injection of contrast material.     

Dynamic gadolinium-enhanced echo-planar MR imaging of the liver: Effect of pulse sequence and dose on enhancement

To develop guidelines for clinical magnetic resonance imaging of the liver, the authors undertook an animal study to investigate the effect of dose and pulse sequence on liver signal intensity in gadopentetate dimeglumine—enhanced echo-planar imaging. Serial imaging of the liver was performed in anesthetized rats after intravenous administration of five different doses (0.01, 0.05, 0.1, 0.2, and 0.5 mmol/kg) of contrast agent, with six different pulse sequences. The results show that gadopentetate dimeglumine—enhanced echo-planar images obtained during the perfusion phase can yield either positive (due to increased T1 relaxation rates) or negative (due to susceptibility-induced increased T2 relaxation rates) liver enhancement depending on choice of pulse sequence and dose. At the current clinically recommended dose of 0.1 mmol/kg, maximal liver signal enhancement was seen with a T1-weighted inversion-recovery sequence, while maximal liver signal diminution was seen with a T2*-weighted gradient-echo sequence. The authors conclude that gadopentetate dimeglumine—enhanced echo-planar imaging can provide T1, T2, and T2* contrast that may be exploited for both lesion detection and lesion characterization.     

Rapidly enhancing hepatic hemangiomas at MRI: Distinction from malignancies with T2-weighted images

The purpose of this study is to describe a subset of atypical hepatic hemangiomas that enhance rapidly and diffusely and to determine whether heavily T2-weighted images could distinguish between atypically enhancing liver hemangiomas and hypervascular malignancies. A retrospective search of MR records identified seven patients with liver hemangiomas that demonstrated diffuse early enhancement and 23 patients with biopsy-proven malignant liver lesions that were hypervascular on dynamic gadolinium-enhanced MR images. Quantitative analysis of signal intensity measurements was performed on the T2-weighted images, heavily T2-weighted (TE < 140), and dynamic gadolinium-enhanced images. Blinded reader comparison of the T2-weighted images and gadolinium-enhanced images was performed. Hypervascular hemangiomas enhanced to a greater degree than hypervascular malignant liver lesions on the early phase gadolinium-enhanced images. Perilesional parenchymal enhancement was demonstrated in five cases of rapidly enhancing hemangiomas. Signal intensity and contrast-to-noise ratios on the heavily T2-weighted images of the hemangiomas were significantly greater than that of the hypervascular malignant lesions (P < .05). Hemangiomas were differentiated from the hypervascular malignant liver lesions with high accuracy (97–100%) by three blinded readers based on the T2-weighted images. A subset of hemangiomas have atypical rapid diffuse enhancement on dynamic gadolinium-enhanced images. These atypical hemangiomas can be distinguished from hypervascular malignant liver lesions on T2-weighted MR images.     

Evaluation of portal MR angiography using superparamagnetic iron oxide

The purpose of our research was to determine the effects of superparamagnetic iron oxide on MR imaging of the portal venous system. Eight piglets were examined in deep anaesthesia and respiratory arrest using a time-of-flight magnetic resonance fast low angle shot, two-dimensional angiography sequence at 1.5T. MR angiograms were acquired precontrast and after intravenous administration of a cumulative dose of 10, 20 and 40 μmol/kg SHU 555A, a superparamagnetic iron oxide contrast agent for MR imaging with a particle size of 60 nm. For each dose, two subsequent sets of scans were obtained and reconstructed by a maximum-intensity-projection algorithm. Hepatic parenchymal and portal venous signal intensities were measured, and portal vein contrast calculated for each set of scans. All examinations were visually rated as to portal vein contrast and homogeneity by two blinded observers. Receiver operating characteristics of both observers were analyzed. The contrast agent reduced hepatic parenchymal signal in a dose-dependent way. After a cumulative dose of 10 μmol iron oxide, hepatic parenchymal signal intensity decreased to 63 ± 6% (average of measurements at 4 and 14 minutes, mean ± standard error of the mean), after 20 μmol to 24 ± 3%, and after 40 μmol to 12 ± 1% of control. Intra-vascular signal in the left main portal vein branch increased to 117 ± 6%, 127 ± 10%, and 133 ± 9% of control, respectively. The contrast-to-noise ratio of the portal vein improved (521 ± 90%, 891 ± 178%, and 995 ± 201% of control in the left portal vein main branch). Intravascular signal intensities increased slightly. The combined effect improved contrast of the portal vein stem and its branches. Receiver operating characteristics analysis documented dose-dependency of contrast medium effects on portal venous contrast and intravascular homogeneity. Visual rating also indicated a positive effect on portal venous contrast. The superparamagnetic iron oxide agent improved portal venous contrast with surrounding hepatic parenchyma in this normal animal model, and could potentially result in more accurate diagnosis of portal venous pathology.     

Use of superparamagnetic contrast media to suppress signal from flowing spins: Preliminary experience

The authors describe their preliminary experience with the use of superparamagnetic magnetic resonance (MR) imaging contrast media for suppression of signal from flowing blood. The goal of this work was to determine if a superparamagnetic contrast agent could successfully eliminate blood signal during cardiac-gated MR imaging, thereby eliminating or reducing flow artifacts associated with the complex and variable hemodynamics within the heart chambers. Imaging and data analysis were performed in 17 dogs subjected to experimental myocardial infarction as part of a parallel project. Six doses (0.2, 1, 2, 3.5, 4, 5, and 10 mg/kg) of AMI-25, an experimental contrast agent, were used in the study. Spin-echo imaging was performed immediately before and every 5 minutes (for an average of 25 minutes) after bolus injection of the contrast agent. Variations in the image signal-to-noise ratio relative to a baseline (before injection of contrast agent) image were assessed as a function of dose and time. Preliminary results suggest that a considerable reduction in blood flow artifacts and, hence, increases in image signal-tonoise ratio can be achieved at doses greater than or equal to 3.5 mg/kg, for approximately 20 minutes after injection. Doses equal to or less than 2 mg/kg and images obtained more than 20 minutes after injection (regardless of dose) did not reliably show hemodynamic artifact suppression.     

Conventional MRA and contrast- enhanced MRA of extracranial vessel segments

Summary The introduction of fast gradient systems allows a reliable visualization of the extracranial carotid vessels by the magnetic resonance angiography (MRA) which meanwhile is implemented into clinical routine. By the mainly applied time-of-flight (TOF) technique, vessels can be imaged without contrast agent (CA). Due to the application of ultra-fast gradient-echo-sequences, the first-pass evaluation of an intravenous bolus-injection of Gadolinium in the carotids from the aortic arch up to the skull base can be performed in less than 30 s. In this study, advantages and disadvantages of both techniques are discussed. For a qualitatively optimal contrast enhanced MRA (CE-MRA) timing parameters like injection delay, flow rate and the adjustment of sequence parameters have to be considered in relation to the fast venous return from the sinus to the jugular veins. First, the optimal time point of the data acquisition have been determined at a model and with a computer simulation in reference to the presence of CA in the arteries. As a result, 90 % of the contrast contribution is defined by 16 % of the symmetrically acquired central k-space lines. A measuring protocol for clinical use was obtained by a gradual variation of spacial resolution, measuring time and CA-injection parameters and was proved in normal volunteers and patients. An exact determination of the bolus-arrival-time by means of a test-bolus injection was acquired. The best qualitative results were achieved by a double-dose injection at 2 ml/s injection rate. The temporal reserves of ultra-fast sequences should be invested in the improvement of the spatial resolution. To date, further investigations related to the problem of optimal CA-application may improve the potentials of CE-MRA procedures.      

High-dose gadoteridol in MR imaging of intracranial neoplasms.

Twelve patients with a high suspicion of brain metastases by previous clinical or radiologic examinations were studied in a phase III investigation with magnetic resonance (MR) imaging at 1.5 T after a bolus intravenous injection of 0.1 mmol/kg gadoteridol followed at 30 minutes by a second bolus injection of 0.2 mmol/kg gadoteridol. All lesions were best demonstrated (showed greatest enhancement) at the 0.3-mmol/kg (cumulative) dose, with image analysis confirming signal intensity enhancement in the majority of cases after the second gadoteridol injection. More lesions were detected with the 0.3-mmol/kg dose than with the 0.1-mmol/kg dose, and more lesions were detected with the 0.1-mmol/kg dose than on precontrast images. In this limited clinical trial, high-dose gadoteridol injection (0.3-mmol/kg cumulative dose) provided improved lesion detection on MR images specifically in intracranial metastatic disease.     

纤维组织粘合剂的实验研究

本文应用“冷沉淀”法制备纤维组织粘合剂。对纤维组织粘合剂中主要成份和含量进行了测定,并测定了主要理化性质,建立了动物实验模型,观察了实验兔对纤维粘合剂的反应。