Identification of cardiac rejection in heterotopic heart transplantation using 111In-antimyosin

It is important in heart transplantation to evaluate precisely the extent and location of cardiac rejection. At present, right ventricular endomyocardial biopsy has been used as the gold standard, however, establishment of noninvasive, simple, and easy diagnostic procedure is desired. The canine donor heart, in which atrial septal defect and tricuspid regurgitation had been produced beforehand, was heterotopically transplanted into the recipient's chest cavity. In seven dogs, two to three mCi of ¹¹¹In-antimyosin was injected intravenously upon cardiac rejection before the heart was excised. ¹¹¹In-antimyosin myocardial imaging was then performed using a gamma camera. In the same slice, a histopathological rejection score was calculated and divided into mild, moderate or severe injection. the uptake of ¹¹¹In-antimyosin was significantly higher in moderate and severe rejected myocardium, since this agent produced a specific and selective localization and concentration in areas of myocardial damage. Therefore, this new technique allows the evaluation of therapeutic intervention upon cardiac rejection and may replace right ventricular endomyocardial biopsy.     

Identification of cardiac rejection in heterotopic heart transplantation using 111In-antimyosin

It is important in heart transplantation to evaluate precisely the extent and location of cardiac rejection. At present, right ventricular endomyocardial biopsy has been used as the gold standard, however, establishment of noninvasive, simple, and easy diagnostic procedure is desired. The canine donor heart, in which atrial septal defect and tricuspid regurgitation had been produced beforehand, was heterotopically transplanted into the recipient's chest cavity. In seven dogs, two to three mCi of 111In-antimyosin was injected intravenously upon cardiac rejection before the heart was excised. 111In-antimyosin myocardial imaging was then performed using a gamma camera. In the same slice, a histopathological rejection score was calculated and divided into mild, moderate or severe injection. The uptake of 111In-antimyosin was significantly higher in moderate and severe rejected myocardium, since this agent produced a specific and selective localization and concentration in areas of myocardial damage. Therefore, this new technique allows the evaluation of therapeutic intervention upon cardiac rejection and may replace right ventricular endomyocardial biopsy.     

移植肝排斥反应血管和胆管改变的MR表现

目的：探讨磁共振血管造影（MRA）和胰胆管成像（MRCP）对诊断肝移植术后排斥反应的价值。方法：6例原位肝移植术（OLT）后排斥反应患者均用磁共振（MR）快速自旋回波（TSE）序列及快速小角度激发梯度回波（FLASH）序列常规扫描、磁共振胆管成像（MRCP）、钆喷替酸葡甲胺（Gd-DTPA）动态增强3D MRA检查,分析各序列图像特点。结果：①形态和信号改变：6例患者均有肝脏体积增大,饱满。仅1例重度急性排斥反应患者肝实质信号异常;②血管异常表现：1例急性排斥反应肝左动脉串珠样改变及供体段门静脉明显变细。1例急性排斥反应肝静脉末梢分支杵状扩张而下腔静脉吻合口通畅。其余4例血管无明显异常表现;③胆管异常表现：4例急性排斥反应患者肝内胆管纤细稀疏,1例肝内胆管未显影,1例无明显异常表现。3例慢性排斥反应患者中2例肝内胆管分支稀疏并左肝管串珠样改变;1例胆总管胆泥形成而肝内胆管未见扩张。结论：肝移植术后排斥反应有一些特征性的血管和胆管MR表现。磁共振血管造影和胆管造影作为一种非侵袭性影像检查方法,可以辅助临床诊断肝移植术后排斥反应。     

The use of xeroradiographic imaging to evaluate fracture repair in avian species

The purpose of the study was to determine how fracture healing occurs in avian species and to document if there are any major differences between medullary and pneumatized bone repair. The avian skeleton with both types of bones in a single species affords an opportunity to evaluate the importance of hemorrhage and bone marrow in the fracture healing process. The general concept of fracture healing in humans is well documented but certain specific aspects of fracture repair remain unclear. Two of these issues are the importance of hemorrhage and the influence of bone marrow in fracture healing. Utilizing correlative studies, we wished to determine if xeroradiographic images reflected histologic changes as healing occurred and to determine if this form of radiographic imaging provides an appropriate monitoring study to assess progress of fracture repair in the clinical circumstance.Correlating the xeroradiographic images with the histologic findings evident of fracture healing was discerned before the actual callus formation occurred. Xeroradiographic imaging was quite helpful in visualizing callus formation and was found to be superior to plain radiographic studies.     

In-111 oxine autologous labeled platelets in the diagnosis of kidney graft rejection

The usefulness of In-111 oxine labeled autologous platelets in the diagnosis of renal graft rejection was studied. The method is based on imaging of the graft area at 4, 24, 48, and 72 hours after the injection of the labeled cells. The study was done in 31 renal transplant recipients. The control group included four patients with normal renal function without evidence of rejection. No platelet uptake was observed in any of them. The study group included 22 patients with acute rejection which was confirmed histologically in 13. One case of chronic vascular type rejection of the graft tracer uptake was seen. There was a false-positive result due to a perirenal hematoma. In three patients with a non-immunological sudden impairment of renal function, no activity was detected in the graft area. We also evaluated the changes in platelet trapping throughout the study and they seemed to correlate with the response to the antirejection therapy.     

Radiographic changes in cardiac contours following heart transplantation. Clarification by MR imaging

Chest radiographs of 46 patients who had undergone heart transplantation were reviewed with special attention to abnormalities of the cardiac contours. MR imaging in 3 such patients revealed 3 types of double right cardiac contours: the recipient right atrium combined with the donor right atrium; the donor right atrium combined with the recipient left atrium; and a cardiac fat pad combined with the right atrium. A prominent main pulmonary artery was shown by MR imaging to result from leftward displacement of the main pulmonary artery caused by clockwise rotation and transverse position of the transplanted heart. Recognition of these unique radiographic appearances is of value in assessing transplanted hearts and in avoiding misdiagnosis.     

MR imaging in assessment of cardiac transplant rejection in humans

To evaluate the efficacy of myocardial T2 values in the assessment of allograft rejection, we performed magnetic resonance (MR) imaging at 0.5 T serially in seven cardiac transplant recipients and singly in seven normal volunteers. Cardiac-gated multi-echo spin echo images were obtained; T2 values were estimated by a two-point method from regions of interest in the myocardium. Patients underwent MR and cardiac biopsy at various times after transplantation. Forty-two patient exams were performed. All biopsies showed either no rejection or early stages of rejection: grade 0 in 8 examinations, grade 1 in 28, and grade 2 in 6. Myocardial T2 values in patients in early stages of cardiac rejection were slightly higher (but not statistically significant) than those in non-rejecting patients and normal volunteers. Although this study did not allow prospective detection of cardiac rejection in our patient group, it demonstrated a trend toward higher T2 values at higher biopsy grades that may indicate an ability to assess more severe stages of transplant rejection.     

201Tl myocardial imaging in a cardiac rejection episode

Serial myocardial imaging using thallium Tl 201 was performed in the early follow-up of two patients with orthotopic cardiac transplantation. In one patient, non-homogeneous uptake, small defects and an irregular myocardial edge were observed during a moderately acute rejection crisis revealed by endomyocardial biopsy. The abnormal gammagraphic findings and histological changes were coincident and exhibited a parallel reversal. We emphasize the connection between these two events. The mechanisms which could explain these phenomena are discussed.     

201Tl Myocardial imaging in a cardiac rejection episode

Serial myocardial imaging using thallium Tl 201 was performed in the early follow-up of two patients with orthotopic cardiac transplantation. In one patient, non-homogeneous uptake, small defects and an irregular myocardial edge were observed during a moderatly acute rejection crisis revealed by endomyocardial biopsy. The abnormal gammagraphic findings and histological changes were coincident and exhibited a parallel reversal. We emphasize the connection between these two events. The mechanisms which could explain these phenomena are discussed.     

The 111In-granulocyte scan in prosthetic vascular graft infections: imaging technique and results

Fourteen patients were examined between 3 weeks and 11 years after implantation of an aortobifemoral vascular graft with 111In labelled leukocytes isolated with discontinuous gradient centrifugation. The camera acquisition was performed with a three phase technique (acquisitions at 30 min, 4 h and 24 h p.i.). The presence and extent of a graft or perigraft infection including complicating fistulas could be correctly diagnosed in six of eight patients with surgically proven infections. Leukocyte uptake index was calculated as 1.77 +/- 0.4 (30 min p.i.) and 2.4 +/- 0.7 (24 h p.i.). All infections could be diagnosed by 30 min p.i., fistulas only could be seen 24 h p.i. In two of eight patients, false positive results were observed. These patients suffered from suspected perigraft hematomas and noninfected aortic graft aneurysms. Both had a negative 30 min scan and a slight uptake in the late scans comparable to bone marrow activity. Six patients with fever of unknown origin showed true negative scans. There were no false negative scans. We conclude that only the leukocyte scan can diagnose the presence and the extent, including fistulas, of vascular graft infections. The three phase technique is recommended to localize the blood pool in the 30 min scan and to diagnose complications 24 h p.i. In cases of a negative 30 min scan and positive 4 h and 24 h scans, false positive results should be suspected. All infections have a leukocyte uptake index higher than 1.2.     

Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and cardiac rejection

Indium-111 antimyosin scans were used to assess myocardial damage in patients with suspected myocarditis and cardiac transplant rejection. The calculation of a myocardium to lung ratio (AM index) to quantify antimyosin uptake was performed. AM index in normal subjects (n = 8) at 48 hr postinjection was 1.46 +/- 0.04. In patients with suspected myocarditis (16 studies in 13 patients), AM index was 2.0 +/- 0.5 (p less than 0.001); suggesting a considerable incidence of ongoing cell damage in this group, despite the small proportion of positive right ventricular endomyocardial biopsy (RVbx) (4/13). In patients studied after cardiac transplantation (37 studies in 17 patients), AM indexes correlated with RVbx. In patients with RVbx proven rejection (n = 14), AM index was 1.87 +/- 0.19 (p less than 0.001). In patients with RVbx showing infiltrates but not myocyte damage (n = 13), AM index was 1.80 +/- 0.27 (p = 0.02). In patients with normal RVbx (n = 10), AM index was 1.56 +/- 0.17 (p = NS versus controls; p = 0.001 versus those with positive RVbx). Calculated AM indexes correlated with graded visual analysis of the scans (r = 0.823; p = 0.001). Antimyosin scans are an appropriate method to assess myocardial damage in patients with suspected myocarditis and cardiac rejection.     

The effects of denervation and acute rejection on left ventricular volumes measured by radionuclide ventriculography following cardiac transplantation in the chacma baboon

Seven baboons underwent autotransplantation of the heart or heart and both lungs (group A). Eleven allografts were performed (group B) (nine orthotopic heart transplants and two en bloc transplants of the heart and both lungs). Radionuclide ventriculography was performed both pretransplant and at intervals posttransplant in all animals, and provided measurements of ejection fraction (EF) and left ventricular volumes (LVv) (end-diastolic volume [EDV], end-systolic volume [ESV], and stroke volume [SV]). In seven animals, a total of 20 endomyocardial biopsies were taken. Correlation was made between histopathological features of acute rejection seen on endomyocardial biopsy and changes in EF and LVv measured by radionuclide imaging. A significant increase of 12% in the EF (P less than 0.01) and significant falls in the LVv were observed in all animals (groups A and B) on the first posttransplant day, presumably a result of total cardiac denervation. EDV was reduced by 50% (P less than 0.005), ESV by 62% (P less than 0.0001), and SV by 43% (P less than 0.0001). In autografted baboons (group A) EF and LVv showed no further changes until reinnervation of the heart had occurred, when they reverted to pretransplant levels. In the allografted baboons (group B) further significant reductions in the LVv occurred as acute cardiac rejection progressed. From the first post-transplant day to the time of the final study before the animals' death, the EF decreased by 10% (P less than 0.01), the EDV by 38% (P less than 0.005), and SV by 73% (P less than 0.003): the decrease in ESV did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of blood-pool subtraction in cardiac indium-111-labeled platelet imaging

Blood-pool subtraction has been proposed to enhance 111In-labeled platelet imaging of intracardiac thrombi. We tested the accuracy of labeled platelet imaging, with and without blood-pool subtraction, in ten subjects with cardiac thrombi of varying age, eight with endocarditis being treated with antimicrobial therapy and ten normal controls. Imaging was performed early after labeled platelet injection (24 hr or less) and late (48 hr or more). Blood-pool subtraction was carried out. All images were graded subjectively by four experienced, "blinded" readers. Detection accuracy was measured by the sensitivity at three fixed levels of specificity estimated from receiver operator characteristic curve analysis and tested by three-way analysis of variance. Detection accuracy was generally improved on delayed images. Blood-pool subtraction did not improve accuracy. Although blood-pool subtraction increased detection sensitivity, this was offset by decreased specificity. For this population studied, blood-pool subtraction did not improve subjective detection of abnormal platelet deposition by 111In platelet imaging.     

Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy

Objective

Comparing the diagnostic value of multi-sequential cardiac magnetic resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac allograft rejection.

Methods

One hundred and forty-six examinations in 73 patients (mean age 53?±?12 years, 58 men) were performed using a 1.5 Tesla system and compared to EMB. Examinations included a STIR (short tau inversion recovery) sequence for calculation of edema ratio (ER), a T1-weighted spin-echo sequence for assessment of global relative enhancement (gRE), and inversion-recovery sequences to visualize late gadolinium enhancement (LGE). Histological grade ≥1B was considered relevant rejection.

Results

One hundred and twenty-seven (127/146?=?87 %) EMBs demonstrated no or mild signs of rejection (grades ≤1A) and 19/146 (13 %) a relevant rejection (grade ≥1B). Sensitivity, specificity, positive predictive, and negative predictive values were as follows: ER: 63 %, 78 %, 30 %, and 93 %; gRE: 63 %, 70 %, 24 %, and 93 %; LGE: 68 %, 36 %, 13 %, and 87 %; with the combination of ER and gRE with at least one out of two positive: 84 %, 57 %, 23 %, and 96 %. ROC analysis revealed an area under the curve of 0.724 for ER and 0.659 for gRE.

Conclusion

CMR parameters for myocarditis are useful to detect sub-clinical acute cellular rejection after heart transplantation. Comparable results to myocarditis can be achieved with a combination of parameters.

Key Points

? Magnetic resonance imaging is useful for the assessment of cardiac allograft rejection. ? CMR has a high negative predictive value for exclusion of allograft rejection. ? Diagnostic performance is not yet good enough to replace endomyocardial biopsy.