Yi Miao

Noninvasive Measurements of Infarct Size After Thrombolysis With a Necrosis-Avid MRI Contrast Agent

BACKGROUND Gadophrin-2 is a new MRI contrast agent with high affinity for necrotic myocardium. The aim of the study was to evaluate whether noninvasive measurements of infarct size after thrombolysis are possible with gadophrin-2-enhanced MRI. METHODS AND RESULTS Coronary artery thrombosis was induced in 3 groups of dogs by the copper-coil technique. Thrombolytic therapy together with aspirin and heparin was initiated after 90 minutes of occlusion. One day (group A), 2 days (group B), or 6 days (group C) after infarction, gadophrin-2 was injected intravenously (50 micromol. kg-1). In vivo T1-weighted segmented turbo-FLASH, in vivo T2-weighted segmented half-Fourier turbo spin echo (HASTE), and T1- and T2-weighted spin-echo MRI of the excised heart were performed 24 hours after gadophrin-2 injection. Regions of strong enhancement were observed on T1-weighted images. Planimetry of short-axis MR images and of corresponding triphenyltetrazolium chloride (TTC)-stained left ventricular (LV) slices showed a close correlation between the enhanced areas and TTC-negative areas for both in vivo (r2=0.98, P<0.0001; mean difference, 0.9+/-2.0% [SD] of the LV volume [LVV]) and postmortem (r2=0.99, P<0.0001; mean difference, 0.9+/-1.4% of LVV) measurements. T2-weighted images overestimated the infarct size by 8.1+/-5.4% of LVV. The mean infarct size was 10.8+/-11.6% of LVV (group A), 22.4+/-11.7% (group B), and 5.1+/-9.3% (group C). CONCLUSIONS In this animal model, in vivo gadophrin-2-enhanced MRI could precisely determine infarct size after thrombolytic therapy. This technique may be very useful for the noninvasive evaluation of infarct size after reperfusion for AMI.

Magnetic resonance imaging-histomorphologic correlation studies on paramagnetic metalloporphyrins in rat models of necrosis

RATIONALE AND OBJECTIVES The authors intended to confirm previous findings that paramagnetic porphyrins are avid only for intratumoral nonviable tissues, but not for viable tumor cells, and to test the hypothesis that necrosis, regardless of location and origin, can be visualized by metalloporphyrin enhanced magnetic resonance imaging (MRI). METHODS Intravenous administrations of gadolinium mesoporphyrin (Gd-MP), manganese tetraphenylporphyrin (Mn-TPP), manganese methylpyrroporphyrin-gadopentetate dimeglumine complex (Mn-MPP-Gd) and manganese tetra(4-sulfonatophenyl)porphyrin (MnTPPS4) at 0.05 mmol/kg were compared with those of gadopentetate dimeglumine (Gd-DTPA) at 0.1 mmol/kg in 38 rats with cholestatic liver necrosis, alcohol- and laser-induced coagulation necrosis in liver, and skeletal muscle, reperfused hepatic infarction, and segmental renal infarction. T1-weighted spin echo MRI (TR/TE = 300/15 mseconds) was acquired before and as long as 48 hours after injection, matched with histologic findings, and correlated with Gd/ Mn tissue content measurements. RESULTS Both Gd-DTPA and the four metalloporphyrins initially caused a similar nonspecific negative contrast enhancement in the necrosis. However, a strong and persisting positive enhancement (necrosis-to-normal contrast ratio ranging from 1.5 to 2.0) developed only with metalloporphyrins in all types of necrosis. In liver and kidney, Gd and Mn concentrations at 24 hours were comparable in necrotic and normal tissues. In muscle, the concentrations were more than eight times higher in necrotic than in normal tissue. CONCLUSIONS The implied affinity of metalloporphyrins for necrosis with presumably increased relaxivity suggests a possible mode of targetability for MRI contrast media that may elicit novel applications.

Treatment of VX2 liver tumor in rabbits with "wet" electrode mediated radio-frequency ablation.

Abstract. Radio-frequency ablation (RFA) has been considered as an alternative therapy for liver tumors. A “wet” electrode with interstitial infusion of hypertonic saline was tested for the RFA of liver tumor in rabbits. Seventy-eight liver tumors (? 1.5 to 3.0 cm) were induced in 41 rabbits by VX2 carcinoma implantation. Fifty-one tumors in 27 rabbits were treated with RFA. Under laparotomy, the RF energy was delivered while 5 % saline was infused through the electrode into the tumor at 1 ml/min. Six rabbits with 12 tumors were treated with only intratumoral 5 % saline infusion without RFA. Another 8 rabbits with 15 tumors received sham operation as untreated controls. The efficacy of the therapy was evaluated with survival rate, MRI, microangiography, and histopathology. In the RFA group, 6 rabbits survived longer than 6 months (absolute eradication rate 22.2 %); 12 rabbits were found free of viable tumor at the moment when they were sacrificed (relative eradication rate 44.4 %); 9 rabbits showed local tumor relapse and/or lung metastasis 2–10 weeks after ablation (recurrent rate 33.3 %). In control groups of saline infusion and sham operation, all 14 rabbits died within 3 months (mortality rate 100 %). Three-month survival rates between RFA group and control groups were significantly different (p < 0.05). Findings of MRI, microangiography, and histology supported these outcomes. Radical treatment of liver malignancy in rabbits is possible with the present modified RFA technique. Its clinical usefulness has to be further proven.

Value of t2-weighted magnetic resonance imaging early after myocardial infarction in dogs: comparison with bis-gadolinium-mesoporphyrin enhanced T1-weighted magnetic resonance imaging and functional data from cine magnetic resonance imaging

Dymarkowski S, Ni Y, Miao Y, et al. Value of T2-weighted magnetic resonance imaging early after myocardial infarction in dogs: comparison with bis-gadolinium-mesoporphyrin enhanced T1-weighted magnetic resonance imaging and functional data from cine magnetic resonance imaging. Invest Radiol 37;2:77–85. Rationale and objectives. Magnetic Resonance Imaging (MRI) has proved to provide noninvasive methods to investigate the functional repercussion of myocardial infarction and to measure infarct size with specific contrast agents. In this study, we evaluate whether the combination of T2-weighted and contrast-enhanced T1-weighted MRI could detect and discern necrotic and ischemic, but salvageable, myocardium. methods. Reperfused myocardial infarction was surgically induced in 14 dogs. T1- and T2-weighted MRI was performed 6 hours after administration of the necrosis avid contrast agent Gadophrin-2 at 0.05 mmol/kg. Gradient-echo cine MRI series were performed at baseline and at 6 hours. Quantification of myocardial infarction was performed with triphenyltetrazolium chloride staining. Results. There was a strong correlation between of postcontrast T1-weighted MRI and histomorphometry (r2 = 0.98, P < 0.01). T2-weighted MRI overestimated the infarct size by 10.5% ± 4.3% of left ventricular area. A good correlation was found between hyperintense areas on T2-weighted images and the percentage of dysfunctional areas on cine MRI (r2 = 0.84, P < 0.01). In regions with increased signal intensity on T2-weighted MRI, a decreased maximal systolic thickening (11.8% ± 4.9%, P = 0.043) was found. conclusion. In this study, the difference between the hyperintense areas on T2-weighted and enhanced T1-weighted images after myocardial infarction likely represents viable myocardium.

Comparison of manganese biodistribution and MR contrast enhancement in rats after intravenous injection of MnDPDP and MnCl2

Purpose: To compare the time course of the MR enhancing properties and biodistri-bution of manganese (Mn) in rats given i.v. Mn dipyridoxyl diphosphate (MnDPDP) or Mn chloride (MnCl2). Material and Methods: Twenty-four adult rats were injected i.v. with 5 μmol/kg MnDPDP or MnCl2, or with 0.5 ml/kg saline. High resolution T1-weighted MR imaging was performed during early (10 min), mid (2 h) and late (24 h) phases after injection. Mn concentrations in major organs were measured by using an ICP-AES technique, and correlated with MR findings. Results: Variable degrees of signal enhancement of major organs observed in MR images corresponded with the amount of Mn uptake after injection of MnDPDP or MnCl2. A prominently lower cardiac, pancreatic and hepatic uptake of Mn was seen at 10 min in rats injected with MnDPDP compared with those given MnCl2 and this was reflected in a difference in signal intensity (SI) in the MR images. At 2 h, the Mn content and SI in the major organs were similar with both MnDPDP and MnCl2. An overall Mn clearance was achieved at 24 h without any important organ retention, with kidney excretion of Mn seen only with MnDPDP. Conclusion: With both MnDPDP and MnCl2, the Mn uptake correlates with the SI enhancement in tissues. The reduced initial cardiac uptake of Mn after MnDPDP treatment compared to MnCl2 may account for the favourable cardiovascular safety of the contrast agent. These data contribute to an understanding of SI enhancement by MnDPDP, and are consistent with other studies showing that at a dose of 5 μmol/kg, MnDPDP can be safely used as a potent MR organ-specific contrast agent.

A novel "cooled-wet" electrode for radiofrequency ablation.

Abstract. In the light of growing demands for improved applicability of radiofrequency ablation (RFA), recently we have developed a novel “cooled-wet” electrode by taking the advantages of both internally cooled and saline-enhanced electrodes. The efficacy of the electrode was evaluated in both ex vivo and in vivo liver RFA under both low and high power output levels. The ablation volume created with the “cooled-wet” electrode appeared to be much larger than that reported up to now with the use of other monopolar electrodes. The mechanisms on how this device optimizes the RF energy delivery are also discussed.

Intracoronary delivery of Gd-DTPA and Gadophrin-2 for determination of myocardial viability with MR imaging

Abstract The aim of this study was to compare intracoronary (i. c.) administration of Gadophrin-2, a necrosis-avid contrast agent (NACA), and nonspecific agent Gd-DTPA for determination of myocardial viability (MV) in acute myocardial infarction (AMI) with MRI. Reperfused AMI was induced in 12 dogs by transcatheter balloon occlusion of coronary artery. In 6 dogs each, Gd-DTPA at 0.1 mmol/kg or Gadophrin-2 at 0.005 mmol/kg was administered into coronary artery by fast bolus (n = 3) or slow infusion (n = 3). Serial ECG-triggered cardiac MRI of T1-weighted segmented turbo fast low-angle shot (FLASH) sequence was conducted and compared with triphenyltetrazolium chloride (TTC) histochemical staining. The contrast ratio and infarct size were quantified and analysed statistically. No cardiovascular side effects were found with local delivery of both agents. After i. c. administration, Gadophrin-2 induced a strong (CR ≥ 1.78) and persistent ( ≥ 10 h) contrast enhancement of infarcted region. The infarct size defined with Gadophrin-2 was almost identical to that with TTC staining throughout the postcontrast period. With a dose 20 times higher, Gd-DTPA also strongly enhanced infarct-to-normal contrast; however, the enhancement diminished with time, i. e. from early strong to later faint enhancement and eventual loss of contrast. The delineated infarct size was also unstable, i. e. from early overestimation to later underestimation and eventual disappearance of the enhanced infarct. In combination with PTCA procedure, i. c. administration of MRI contrast agents may prove useful for post-procedure verification of diagnosis. The NACA-enhanced MRI may serve as an in vivo surrogate of postmortem histochemical staining for determination of MV. Although applicable in clinical setting, cardiac MRI with nonspecific Gd-DTPA is less reliable and should be performed within less than 1 h after contrast.

MRI contrast enhancement of necrosis by MP-2269 and gadophrin-2 in a rat model of liver infarction

Ni Y, Adzamli K, Miao Y, et al. MRI contrast enhancement of necrosis by MP-2269 and gadophrin-2 in a rat model of liver infarction. Invest Radiol 2001;36:97–103. rationale and objectives. The mechanisms of action leading to specific localization of necrosis-avid contrast agents (NACAs) such as gadophrin-2 are not well defined. It has been suggested recently that agents with a high degree of serum albumin binding may also serve as NACAs by virtue of nonspecific hydrophobic interactions. The present MRI-histomorphology correlation study was conducted to verify the likelihood of the proposed albumin-binding mechanism by comparing an albumin-binding blood pool agent, MP-2269, with gadophrin-2 in a rat model of reperfused liver infarction. methods.Reperfused infarction in the right liver lobe was surgically induced in six rats. Serial T1-weighted MRI was performed before and after intravenous injection of MP-2269 at 0.05 mmol/kg and repeated in the same rats 24 hours later after intravenous injection of gadophrin-2 at the same dosage (0.05 mmol/kg). The MR images were matched with corresponding histomorphological findings. The signal intensity and contrast ratio of infarcted and normal hepatic lobes were quantified and compared between the two agents during the postcontrast course. results.Before contrast, the infarcted lobe was indiscernible from normal liver on T1-weighted MRI. Shortly after injection of both MP-2269 and gadophrin-2, a negative contrast occurred between infarcted and normal liver because of a strong liver signal intensity enhancement and an inferior uptake in the necrotic liver. On delayed phase (>60 minutes), a necrosis-specific contrast enhancement (contrast ratio 1.6) developed with gadophrin-2 but not with MP-2269. The MR images matched well with corresponding histomorphological findings. conclusions.Although both MP-2269 and gadophrin-2 feature an albumin-binding capacity, only gadophrin-2 displayed a persistent necrosis-specific contrast enhancement in the rat model of reperfused liver infarction. Therefore, the role of albumin binding in the mechanisms of NACAs should be reevaluated.

Evaluation of Radiofrequency Ablation as an Alternative for the Treatment of Brain Tumor in Rabbits

Radiofrequency ablation (RFA) has emerged recently as a promising therapy for extracranial malignancies. This experiment was conducted to explore the potential of RFA for the treatment of brain tumor in a rabbit model with imaging–histological assessment.Eighteen rabbits with intracranially implanted VX2 tumors of 0.9 ± 0.2 cm in diameter were divided into two groups. Group A (n=12) was treated with a cooled-tip RFA technique at 30 watts for 30–60 s. Group B (n=6) received sham operation. The therapeutic efficacy was evaluated by comparing survival rate, magnetic resonance imaging (MRI) and histological findings.All animals in Group B died within one month after tumor implantation (19 ± 2.6 days). Tumor eradication was achieved in 6/12 rabbits (50.0%) in Group A, of which three rabbits survived longer than three months, another three rabbits were found free of viable tumor when sacrificed. Five rabbits suffered from local tumor relapse. One rabbit developed intracranial metastasis to the brain stem despite a complete ablation of the original tumor. Three-month survival rate of RFA treated rabbits was significantly higher (p < 0.05) than that of control rabbits. The typical MRI appearances of the acute RFA lesion consisted of three characteristic concentric zones, which corresponded to central coagulative tissues (Zone A), peripheral hemorrhagic rim (Zone B) and interstitial edema (Zone C) on histology.This study suggests that RFA may become a promising alternative therapy for the treatment of brain tumor. The recognized characters of thermal lesion on MRI and histology may prove valuable in delimitating the ablation range and understanding the biological response of the RFA.

Comparison of iron oxide particles (AMI 227) with a gadolinium complex (Gd-DOTA) in dynamic susceptibility contrast MR imagings (FLASH and EPI) for both phantom and rat brain at 1.5 Tesla

The goal of the study was to compare, in phantom and normally perfused rat brain tissue, a superparamagnetic iron oxide particle‐based contrast agent (AMI 227) with a low‐molecular‐weight gadolinium chelate, gadolinium tetraazacyclododecanetetraacetic acid (Gd‐DOTA), in two susceptibility contrast magnetic resonance imaging (MRI) modes [fast low‐angle shot sequence (FLASH) and echoplanar imaging (EPI)]. A phantom consisting of dilution series of both contrast agents was manufactured. Dilutions were obtained with isotonic serum from the available agent solutions (0.5 mmol Gd/mL Gd‐DOTA; 350 μmol Fe/mL AMI 227). Eighteen rats were studied. Contrast agent (0.1 mL) was bolus injected in each rat, and dynamic MRI was performed (first pass of the contrast agent) in rat brain. The doses of AMI 227 injected were extrapolated from the phantom experiment: 0.2 mmol/kg body weight of Gd‐DOTA and 7, 14, and 28 μmol Fe/kg body weight of AMI 227 were injected.