Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.     

The role of ultrasound in the diagnosis of kidney allograft rejection.

Seventeen nephrectomized dogs underwent kidney transplantation from unrelated donors. Routine immunosuppressive therapy was administered. Serial ultrasound studies and biopsies and complete pathological examinations were performed and compared. A number of sonographic changes were observed within the renal parenchyma during rejection, some of which were present before a significant rise in serum creatinine levels. The medulla became enlarged due to edema, followed by growth of the rest of the kidney and thickening of the cortex. The cortical echoes became more sparsely distributed and either increased or decreased in amplitude; distribution was generalized or localized. During rejection, the corticomedullary boundary became indistinct. Later, a decrease in the renal sinus echoes was also noted. In 2 cases, perirenal fluid collections occurred as the result of renal rupture.     

肝脏移植术后体液性排斥反应的诊断与治疗

目的寻找体液因素参与肝脏移植排斥反应的相关证据,探索临床监测和治疗体液性排斥反应的合理方案。方法通过检测肝脏移植术后肝穿组织中补体C4d、CD20(B细胞)和CD138(浆细胞)的表达情况,诊断肝损伤患者是否存在体液性排斥反应。临床结合病理诊断为排斥反应时,首先增加他克莫司(普乐可复)用量,肝功能损害严重者采用激素冲击治疗;诊断为体液性排斥反应的患者激素冲击治疗无效后,给予抗胸腺细胞球蛋白(ATG)或雷帕霉素(RPM)治疗。结果16例患者共进行25次肝脏穿刺检查,病理检查结合临床表现,10例患者诊断为体液性排斥反应15次,4例患者诊断为细胞性排斥反应6次,另外2例患者均先后诊断为急性和慢性排斥反应。体液性排斥反应激素冲击治疗有效率(29.4%,5/17)明显低于细胞性排斥反应(87.5%,7/8)。7例患者12次肝损害时诊断为耐激素性体液性排斥反应,在激素冲击治疗无效后1例给予ATG治疗,5例加用RPM,排斥反应均得以纠正,另外1例接受"O"型供肝的"AB"型患者出现2次肝功能明显异常,采取多种治疗方法无效,最终因肝功能衰竭死亡。结论体液免疫因素可能参与了部分肝脏移植急、慢性排斥反应的发生。应用ATG和RPM治疗体液性排斥反应较为有效。     

Myocardial high-energy phosphate metabolism and allograft rejection in patients with heart transplants

To determine whether myocardial high-energy phosphate metabolism is altered in cardiac allograft patients undergoing rejection, 14 patients with heart transplants were examined with image-guided, one-dimensional, phase-encoded surface-coil phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy on 19 occasions 39-2,021 days after transplantation. On average, patients underwent mild rejection (detected with endomyocardial biopsy) and had a reduced ratio of anterior myocardial phosphocreatine (PCr) to adenosine triphosphate (ATP) (1.57 +/- 0.50 [standard deviation] vs 1.93 +/- 0.2; P less than .01) compared with that of 17 healthy control subjects. Ratios of PCr to inorganic phosphate also appeared lower whenever detectable. However, P-31 NMR spectroscopy did not permit reliable identification of patients who required augmented therapy for rejection detected with biopsy either on the day of the P-31 NMR spectroscopic study or at the next scheduled biopsy 10-140 days thereafter (sensitivity, 50%, and specificity, 73% with use of cardiac-averaged PCr/ATP values for each heart; sensitivity, 88%, and specificity, 55% with use of the lowest myocardial PCr/ATP ratios measured in each heart).     

Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantation.

Anatomical and functional information (renography, perfusion) was obtained by MRI in a life-supporting transplantation model, in which Lewis rats received kidneys from Fisher 344 donors. Renography and perfusion analyses were carried out with Gd-DOTA and small particles of iron oxide (SPIO), respectively. Starting 12 weeks posttransplantation, images from grafts of untreated recipients exhibited distinctive signal attenuation in the cortex. Animals treated with cyclosporin (Sandimmune Neoral; Novartis Pharma, Basel, Switzerland) to prevent acute rejection showed a signal attenuation in the cortex at 33 weeks posttransplantation, while kidneys from rats treated additionally with everolimus (Certican; Novartis), a rapamycin derivative, had no changes in anatomical appearance. A significant negative correlation was found between the MRI cortical signal intensity and the histologically determined iron content in macrophages located in the cortex. Renography revealed a significantly reduced functionality of the kidneys of untreated controls 33 weeks after transplantation, while no significant changes in perfusion were observed in any group of rats. These results suggest the feasibility, by labeling macrophages with SPIO, of detecting signs of graft rejection significantly earlier than when changes in function occur. Monitoring early changes associated with chronic rejection can have an impact in preclinical studies by shortening the duration of the experimental period and by facilitating the investigation of novel immunomodulatory therapies for transplantation.     

Evaluation of portal circulation in rats by rectal administration of 201Tl followed by intrasplenic injection of 51Cr-labeled microspheres

The heart-to-liver (H/L) uptake ratio in rats was determined 8 min after the rectal administration of ²⁰¹Tl. Apart from normal controls, three groups of rats were examined; these were composed of animals with induced (1) acute hepatic damage, (2) liver cirrhosis, and (3) partial portal-vein ligation. After the rectal administration of ²⁰¹Tl, ⁵¹Cr-labeled microspheres were injected into the spleen. The radioactivity of the removed liver, lungs, and heart was determined in a gamma-well scintillation counter, and the radioactivity of ²⁰¹Tl and the ⁵¹Cr-labeled microspheres was separately calculated using simultaneous equations derived from the results of a preliminary experiment. The H/L ratios (²⁰¹Tl) in the normal controls and the animals with acute hepatic damage were not significantly different; however, there was a positive correlation (P0.01) between the H/L ratio and the shunt index (⁵¹Cr microspheres) in three groups, i.e., normal controls, liver cirrhosis, and partial portal-vein ligation.     

超声造影在移植肾排斥反应中的诊断价值

目的观测移植肾排斥反应的超声造影特点,分析造影图像,寻求超声造影诊断移植肾排斥反应的定量指标。方法选取患者30例,将患者分为A、B两组,A组20例肾功能异常和B组10例移植肾功能正常患者分别进行常规超声检查和超声造影检查,观察造影时微循环灌注情况并应用造影分析软件对感兴趣区域分析定量指标曲线下面积AUC(Area Under The Curve),然后进行统计分析。结果 A组移植肾微循环的灌注明显比B组差;A组与B组的分析指标AUC差异有统计学意义(P<0.05)。结论超声造影可以动态检测移植肾发生排斥反应时微循环灌注的改变;定量指标AUC为诊断移植肾排斥反应提供了较为可靠、客观的影像学依据。     

Evaluation of portal circulation in rats by rectal administration of 201Tl followed by intrasplenic injection of 51Cr-labeled microspheres

The heart-to-liver (H/L) uptake ratio in rats was determined 8 min after the rectal administration of 201Tl. Apart from normal controls, three groups of rats were examined; these were composed of animals with induced (1) acute hepatic damage, (2) liver cirrhosis, and (3) partial portal-vein ligation. After the rectal administration of 201Tl, 51Cr-labeled microspheres were injected into the spleen. The radioactivity of the removed liver, lungs, and heart was determined in a gamma-well scintillation counter, and the radioactivity of 201Tl and the 51Cr-labeled microspheres was separately calculated using simultaneous equations derived from the results of a preliminary experiment. The H/L ratios (201Tl) in the normal controls and the animals with acute hepatic damage were not significantly different; however, there was a positive correlation (P less than 0.01) between the H/L ratio and the shunt index (51Cr microspheres) in three groups, i.e., normal controls, liver cirrhosis, and partial portal-vein ligation.     

Deceased vs. living donor kidney transplantation in prediction of acute renal allograft rejection using Tc-99m DTPA renal scan

Annals of Nuclear Medicine - No data are available regarding different prognostic values of Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scan in kidney transplantation (KT) recipients...     

Duplex doppler ultrasound in the diagnosis of acute renal allograft rejection

As renal transplantation becomes more commonplace and successful, there is an increasing demand for non-invasive methods of studying possible complications. One hundred and fifty-four duplex Doppler sonography scans were performed in 38 patients within 52 days of receiving a renal allograft. Renal vascular impedance was estimated in the intrarenal arteries by calculating the resistive index ([peak systolic frequency shift--lowest diastolic frequency shift]/peak systolic frequency shift). A resistive index of greater than 0.80 was very suggestive of rejection (positive predictive value 82%); with a value of less than 0.70 rejection was unlikely (negative predictive value, 98%).     

19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells

Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure.We have previously shown that cellular magnetic resonance imaging (MRI) of iron‐oxide labeled immune‐cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T‐weighted images. In this study, we tested the feasibility of using a fluorine‐based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine‐19 (¹⁹F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro‐15‐crown‐5‐ether, we observed ¹⁹F‐signal intensity in the organs experiencing rejection by ¹⁹F MRI, and conventional ¹H MRI was used for anatomical context. Immunofluorescense and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, ¹⁹F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.