Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy.

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

Diagnosis of chest wall invasion by lung cancer: useful criteria for exclusion of the possibility of chest wall invasion with MR imaging.

PURPOSE: To compare the accuracy of thin-section CT, conventional static MR imaging (conventional MRI), and breathing dynamic echo planar magnetic resonance imaging (BDEPI) in evaluating lung cancer invasion to the chest wall. MATERIALS AND METHODS: Thin-section CT, conventional MRI, and BDEPI were performed preoperatively in 20 patients suspected of having primary lung cancers adjacent to the chest wall on conventional CT. The results of imaging findings were compared with those of surgical and histopathological findings. RESULTS: All patients were confirmed to have no chest wall invasion after surgery. By thin-section CT, 10 of 20 patients were correctly diagnosed as having no chest wall invasion (50% specificity). Two of the 20 patients were incorrectly diagnosed as having chest wall invasion by conventional MRI and BDEPI (90% specificity). CONCLUSION: When chest wall invasion is suspected on CT scans, static and breathing dynamic MRI are recommended to avoid false positive interpretations.

Heavily T1-weighted images without respiratory artifacts: partial angle inversion recovery fast spin-echo imaging (PAIR-FSE).

We obtained T1-weighted images in the abdominal region using the partial angle inversion recovery fast spin echo (PAIR-FSE) with the respiratory triggering (RT) method and compared the image quality with that of conventional SE (TR/TE 500/10 msec) with the partial angle inversion recovery (PEAR) method. The signal difference to noise ratio of the PAIR-FSE was 1.6 times higher (6.94 +/- 3.08) than that of SE (4.30 +/- 1.88). Respiratory motion-induced ghost artifacts were reduced by half in PAIR-FSE with RT (1.01 +/- 0.47) in comparison with SE with PEAR (2.24 +/- 0.70). J. Magn. Reson. Imaging 2000;12:960-964.

Detection of minute pleural fluid in the pleural retracted space associated with peripheral lung cancer: evaluation with MR imaging.

PURPOSE: To evaluate the efficacy of magnetic resonance imaging (MRI) in detecting minute pleural fluid in the pleural retracted space (PRS) associated with peripheral lung cancer. MATERIALS AND METHODS: Our subjects were 20 patients with peripheral lung cancer in whom thin-section CT in the lung window setting demonstrated lesions adjacent to the pleural surface, and who were referred for MR imaging. The imaging findings were retrospectively evaluated and correlated with the histopathologic specimens. Pleural fluid was aspirated for cytology under ultrasound (US) guidance in six patients. RESULTS: STIR MR images revealed water SI areas beneath the chest wall associated with the lung cancer, whereas, on CT images, lung cancer and minute pleural fluid in the PRS showed similar soft-tissue density without enabling easy differentiation. Two of the six patients who underwent aspiration cytology showed malignancy. All histopathologic specimens obtained from 18 patients who underwent surgery showed pleural retraction corresponding to the water SI areas on STIR images. Histopathological study revealed that the fibrotic focus of the tumor tended to occur more intensively when the shape of pleural retraction was thinner and deeper. CONCLUSION: Water SI areas on STIR images were thought to suggest pleural fluid retention in the PRS. MRI was sensitive in detecting minute pleural fluid in the PRS and may help to avoid overdiagnosis of chest wall invasion induced from peripheral lung cancers.

The contributory role of interstitial water in Gd-DTPA-enhanced MRI in myocardial infarction.

We studied the mechanism underlying regional enhancement of myocardial infarction using T1-weighted MRI with gadolinium (Gd)-DTPA. Anterior myocardial infarction (MI) was produced by left anterior descending coronary artery ligation in three groups of rats as follows: 60 minutes occlusion (occlusion group, N = 6), 60 minutes occlusion plus 120 minutes reperfusion (reperfusion group, N = 8), and sham-operated (control, N = 6). In Gd-DTPA-enhanced MRI, MI was demarcated as a hypoenhanced region in the occlusion group and as a homogeneous hyperenhanced region in the reperfusion group. Both Gd-DTPA tissue concentration and tissue water content in the anterior wall were highest in the reperfusion group (P<0.05), a finding suggestive of microscopically observed interstitial edema. The data suggest that regional accumulation of Gd-DTPA in the reperfused group can be explained by increased interstitial water content, contributing to the delayed washout of the water-soluble contrast medium.

Hemorrhagic myocardial infarction after coronary reperfusion detected in vivo by magnetic resonance imaging in humans: prevalence and clinical implications.

With the advent of thrombolytic therapy, hemorrhagic myocardial infarction (HMI) has been observed in experimental and human autopsy studies. However, its clinical implications remain undetermined, because of the absence of a reliable method to detect its presence in vivo. This study was designed to evaluate the clinical implications of HMI detected by magnetic resonance (MR) imaging in vivo after coronary reperfusion. Thirty-nine patients with acute myocardial infarction (AMI) were studied. Percutaneous transluminal coronary angioplasty (PTCA) was used to reopen the occluded coronary artery. Electrocardiogram (ECG)-gated T2*-weighted gradient-echo MR imaging was performed to detect intramyocardial hemorrhage, using a 1.5-T magnet within 2 weeks after coronary reperfusion (average, 5.7 days). Thirteen patients (33%) showed intramyocardial hemorrhage as a distinct hypointense zone by gradient-echo MR imaging and 26 patients showed homogeneous intensity consistent with absence of intramyocardial hemorrhage. Coronary angiograms showed lesser development of collateral flow in the patients with HMI than in those without (81% vs. 37%). Infarct size, estimated 1 month after coronary reperfusion by thallium-201 scintigraphy, was larger among patients with HMI than in those without (37 +/- 14% vs. 21 +/- 14%, respectively, p < 0.05). Left ventricular ejection fraction at 1 month follow-up showed less recovery in patients with HMI than in those without (47 +/- 9 to 51 +/- 10%; p = 0.47, vs. 53 +/- 10 to 60 +/- 9%, respectively, p < 0.05). ECG-gated T2*-weighted gradient-echo MR imaging offers a noninvasive means of detection of intramyocardial hemorrhage in patients with reperfused AMI. HMI occurred even after primary PTCA and may be a common finding associated with severely injured myocardium.

Beneficial effect of salmon roe phosphatidylcholine in chronic liver disease.

Phosphatidylcholine (PC), especially dilinoleoyl-PC, has been reported to be effective in preventing hepatic fibrosis in chronically alcohol-fed baboons. Continuous hepatic inflammation predisposes the structure of the liver to fibrosis. Since n-3 polyunsaturated fatty acids (PUFA) have been shown to exhibit an anti-inflammatory effect, we tested the hypothesis that n-3 PUFA PC as a dietary supplement has a beneficial effect on chronic liver disease susceptible to fibrosis. Salmon roe phospholipids, 90% of which are PC, were extracted and encapsulated. Almost a third of the PC fatty acids were docosahexaenoic acid (22:6 n3) and 10% were eicosapentanoic acid (20:5 n3). About 1600 mg/day of the phospholipids was administered for six months to six chronic liver disease patients, four with hepatitis B infection (three with cirrhosis, one with chronic hepatitis), one with hepatitis C virus cirrhosis and one with alcoholic cirrhosis. There was no change in the results of blood chemistry studies related to liver function, except in globulin, which decreased from 3.80 g/dl to 3.67 g/dl (p < 0.05). Among the lipid parameters, HDL-cholesterol, apolipoprotein A-I and apolipoprotein E increased significantly. Although this was a small trial, n-3 PUFA PC may be beneficial in the treatment of chronic liver diseases.

[Myocardial wall motion analysis with phase shift imaging: cine phase contrast technique].

MR imaging can be used to measure proton velocity directly as a phase shift with the bipolar gradient method. This method is applied in MR angiography as a phase contrast(PC) technique. We attempted to evaluate myocardial motion utilizing the PC technique. With the cine PC technique, 16-cardiac phased 3D velocity images of the myocardium were obtained. In normal subjects, the myocardial velocity throughout the cardiac cycle were changes regular in space as well as in time, and there was no inconsistency between the motion directions. Whereas, in cases with myocardial infarction, 3D velocity images revealed some regions with zero velocity and/or some regions which showed reverse direction motions compared with the surrounding normal myocardium.

Two-dimensional time-of-flight MR venography: assessment with detection of chronic deep venous thrombosis in combination with magnetization transfer contrast.

PURPOSE: The purpose of this study was to determine the optimum imaging parameters for 2D-TOF MR venography (MRV) of the pelvis and suprapopliteal deep venous system in combination with off-resonance magnetization transfer constant (MTC) and to evaluate the use of MRV in patients suspected of having chronic deep venous thrombosis (DVT) by comparing its accuracy with that of conventional venography (CV). METHOD: MRV was performed in 10 normal subjects to determine the optimum imaging parameters. Systematically varied scan parameters included flip angles ranging from 30 to 120 degrees by 10 degrees increments. Best TR was calculated by using the theoretical relation between the optimal TR and flow velocity. We then evaluated the use of MRV in 26 patients (total 52 deep venous systems) suspected of having chronic DVT by comparing its accuracy in evaluating the intrapelvic and suprapopliteal deep venous system with that of CV. RESULTS: The optimal imaging parameters for intrapelvic and suprapopliteal venous system MRV were found to be a flip angle of 60 degrees and a pulse sequence of 35/6.9 (TR ms/TE ms) combined with an off-resonance MTC technique. All the main veins of the intrapelvic and suprapopliteal venous systems were clearly demonstrated in each subject. The sensitivity of MRV was 100% and its specificity was 100% for diagnosis of pelvic venous stenosis. The collateral vessels were demonstrated with MRV in all patients. CONCLUSION: 2D-TOF off-resonance MTC MRV of the pelvis and the suprapopliteal lower extremities is suitable for evaluation of intrapelvic branches and suprapopliteal deep venous system and chronic DVT.

The relationship between lipoprotein(a) and low density lipoprotein receptors during the treatment of hyperthyroidism.

To determine whether the low density lipoprotein (LDL) receptor pathway is involved in the catabolism of plasma lipoprotein (a) [Lp(a)], serum lipids, Lp(a), and LDL receptor activity were measured in seven patients with hyperthyroidism before and after methimazole treatment given hyperthyroidism is associated with enhanced LDL receptor activity. LDL receptor activity in patients was estimated by the equation using the serum concentrations of apolipoprotein (apo) B and C-II. When euthyroidism was achieved after treatment, not only did serum total cholesterol, high density lipoprotein-cholesterol, apo B, and LDL-cholesterol (LDL-Ch) levels rise, but Lp(a) significantly increased and calculated LDL receptor activity significantly decreased. The changes in LDL receptor activity were significantly correlated with the changes in LDL-Ch as expected, but not with changes in Lp(a). These results suggest that the serum concentration of Lp(a) is lowered in hyperthyroidism, probably by a mechanism other than the enhanced activity of the LDL receptor, and that the LDL receptor pathway is involved in the catabolism of Lp(a) to a limited extent.

Evaluation of tissue plasminogen activator and plasminogen activator inhibitor-I levels in acute myocardial infarction.

Fluctuations in tissue plasminogen activator (t-PA) activity, t-PA antigen, and plasminogen activator inhibitor-I (PAI-1) antigen levels were evaluated in blood samples obtained from 84 patients with initial uneventful acute myocardial infarction (AMI) and 35 patients with reinfarction and fatal infarction (patients with bad prognoses). Patients with initial AMI had significantly higher levels of t-PA activity than those of 14 patients with angina pectoris. Tissue plasminogen activator activity peaked between day 7 and 19 after the initial attack of AMI. Plasminogen activator inhibitor-I antigen level decreased significantly between day 2 and 19, then returned to the baseline levels of patients with angina pectoris nearly 4 weeks later. The t-PA activity levels of patients with reinfarction were significantly lower than those in patients without events between day 0 and 3 and between day 7 and 19. The percentage stenosis in the coronary arteries measured by coronary angiography was negatively correlated with t-PA activity. This information may help in selecting aggressive treatments such as thrombolysis by recombinant t-PA and predicting the prognosis for patients with AMI.

T1-weighted images with ECG gating using partial flip angle spin-echo imaging.

ECG-gated spin-echo imaging can reduce vascular artefacts compared with spin-echo scans without gating. However, this method produces poor T1-weighted images because the repetition time (TR) is limited by the heart rate. We investigated the value of low flip angle spin-echo imaging for increasing T1-dependent contrast when using ECG gating. Using computer simulation, the predicted contrast increased with decreasing the flip angle, and the effect was almost saturated at a flip angle of around 40 degrees. With the application of this flip angle, the identical image contrast as a T1-weighted image (TR = 400 ms) can be obtained within the heart rate range of 65 to 75 beats/min. For clinical evaluation, the tissue contrast index values ((signal intensity in the lesion-signal intensity in the muscle)2 x 100/signal intensity in the muscle) obtained by conventional spin-echo and low flip angle spin-echo imaging were compared in 17 patients. The contrast index of low flip angle spin-echo images (74.0 +/- 52.0) was significantly higher than that of conventional spin-echo images (40.9 +/- 35.9). Thus, ECG-gated low flip angle spin-echo imaging provided better T1-dependent contrast than conventional ECG-gated spin-echo imaging. This method may be especially useful for Gd-DTPA-enhanced magnetic resonance imaging.

Intrapelvic two-dimensional time-of-flight magnetic resonance angiography in healthy and diseased subjects.

We evaluated the use of magnetic resonance angiography (MRA) based on two-dimensional (2D) time-of-flight (TOF) technique in the pelvic vasculature. In the initial phase of this study, MRA was performed in 10 normal subjects for determination of the optimum imaging parameters. Systemically varied scan parameters included flip angle ranging from 20 degrees to 90 degrees by 10 degrees increments and repetition time (TR) of 30, 40, and 50 ms. The optimum imaging parameters for intrapelvic MR angiography were found to be flip angle of 90 degrees, pulse sequence of 30/4.9 (TR ms/TE ms). Using these imaging parameters, 70-100% of the second division branches of the internal iliac artery could be visualized in each subject. In the second phase of this study, we evaluated the use of MR angiography in patients with intrapelvic vascular disease by comparing its accuracy in evaluating the iliac arteries with that of conventional angiography. In patients with atheromatous disease, the MR angiographic determination was consistent with that of conventional angiography in 23 of 28 visualized arterial segments (82%). In eight lesions in patients with non-stenotic vascular disease or hypervascular pelvic tumours, all lesions were demonstrated clearly with MR angiography. 2D TOF technique with high flip angle excitation is suitable for the evaluation of main iliac branches and diseased vessels.

Quantification of occlusive and reperfused myocardial infarct size with Gd-DTPA-enhanced MR imaging.

The potential of Gd-DTPA-enhanced magnetic resonance imaging (MRI) for measuring infarct size was assessed in canine hearts. Twelve dogs underwent pre- and post-contrast MR imaging before and after recanalization. Infarct area was identified by triphenyltetrazolium chloride (TTC) staining of postmortal specimens in each case. Recanalization was complete in 10 dogs. High SI area was seen after reperfusion in nine of them; and it showed low signal intensity before reperfusion in seven of them. Two dogs were killed during reperfusion period: neither of them showed a low SI area before reperfusion. Necrotic regions were confirmed by TTC staining in seven of 12 dogs. Both the visual and quantitative assessment (n = 7) indicated that the extent of the low SI area before reperfusion was approximately the same as that of the necrotic region shown by TTC staining, while the high SI area seen after reperfusion was obviously larger than both the necrotic region and the low SI area on pre-reperfusion images. The correlation coefficient between low SI area and necrotic area was 0.98, and between high SI area and necrotic area was 0.80. These results suggest that Gd-DTPA-enhanced MRI may be useful for quantification of infarct size in occlusive myocardial infarction but it may overestimate in reperfused one.

[Low flip angle spin-echo MR imaging to obtain better Gd-DTPA enhanced imaging with ECG gating].

ECG-gated spin-echo imaging (ECG-SE) can reduce physiological motion artifacts. However, ECG-SE does not provide strong T1-weighted images because repetition time (TR) depends on heart rate (HR). We investigated the usefulness of low flip angle spin-echo imaging (LFSE) in obtaining more T1-dependent contrast with ECG gating. in computer simulation, the predicted image contrast and signal-to-noise ratio (SNR) obtained for each flip angle (0-180 degrees) and each TR (300 msec-1200 msec) were compared with those obtained by conventional T1-weighted spin-echo imaging (CSE: TR = 500 msec, TE = 20 msec). In clinical evaluation, tissue contrast [contrast index (CI): (SI of lesion-SI of muscle)2*100/SI of muscle] obtained by CSE and LFSE were compared in 17 patients. At a TR of 1,000 msec, T1-dependent contrast increased with decreasing flip angle and that at 38 degrees was identical to that with T1-weighted spin-echo. SNR increased with the flip angle until 100 degrees, and that at 53 degrees was identical to that with T1-weighted spin-echo. CI on LFSE (74.0 +/- 52.0) was significantly higher than CI on CSE (40.9 +/- 35.9). ECG-gated LFSE imaging provides better T1-dependent contrast than conventional ECG-SE. This method was especially useful for Gd-DTPA enhanced MR imaging.

Monoclonal antibodies to poly(adenosine diphosphate ribose) recognize different structures.

Two hybridomas producing monoclonal antibodies to poly(adenosine diphosphate ribose) [poly(ADP-Rib)] were established. One antibody, 10H (IgG3, kappa), bound to most of the poly(ADP-Rib) preparation, which consisted of molecules of various sizes of more than 20 ADP-Rib residues. The binding of this antibody was inhibited by not only poly-(ADP-Rib) but also a monomer unit of poly(ADP-Rib), Ado(P)-Rib-P. The sites protected by antibody 10H were isolated and analyzed by hydrolysis with alkaline phosphomonoesterase and then snake venom phosphodiesterase. The sites contained the same amounts of monomer units and branched portions [Ado(P)-Rib(P)-Rib-P] as the original poly(ADP-Rib) molecules but a lower average number of branched portions per molecule than in the original molecules. The other antibody, 16B (IgM, lambda), reacted with only 50% of the radioactive poly(ADP-Rib), and its binding was not inhibited by a monomer unit. This antibody protected 25% of all the poly(ADP-Rib) molecules from hydrolysis by snake venom phosphodiesterase. The protected sites contained twice as many branched portions per molecule as the original poly(ADP-Rib) molecules. These results show that the two monoclonal antibodies recognize different structures of poly-(ADP-Rib); 10H antibody recognizes the linear structure with ribose-ribose linkages, and 16B antibody may recognize specific structures, including the branched portions of poly-(ADP-Rib).

Enhancement of antitumor activity of bleomycin by benzamide in vitro and in vivo.

The cytotoxic effects of bleomycin on HeLa cells in culture were enhanced by incubation of the cells with benzamide, a potent inhibitor of poly(ADP-ribose) polymerase, at concentrations at which benzamide alone did not show any cytotoxicity. Benzamide plus bleomycin display enhanced therapeutic effects against Ehrlich ascites tumor cells in vivo. On daily treatment with various doses of bleomycin plus benzamide for 10 days, mice with Ehrlich ascites tumors survived longer than mice on treatment with bleomycin alone.