Jan Bucerius

Diagnostic Performance of Whole Body Dual Modality 18F-FDG PET/CT Imaging for N- and M-Staging of Malignant Melanoma: Experience With 250 Consecutive Patients

Purpose To assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) for N- and M-staging of cutaneous melanoma. Patients and Methods This is a retrospective and blinded study of 250 consecutive patients (105 women, 145 men; age 58 ± 16 years) who underwent FDG-PET/CT for staging of cutaneous melanoma at different time points in the course of disease. Whole-body FDG-PET/CT was performed 101 ± 21 minutes postinjection of 371 ± 41 MBq FDG. Diagnostic accuracy for N- and M-staging was determined for CT alone, PET alone, and PET/CT. Results PET/CT detected significantly more visceral and nonvisceral metastases than PET alone and CT alone (98.7%, 88.8%, and 69.7%, respectively). PET/CT imaging thus provided significantly more accurate interpretations regarding overall N- and M-staging than PET alone and CT alone. Overall N- and M-stage was correctly determined by PET/CT in 243 of 250 patients (97.2%; 95% CI, 95.2% to 99.4%) compared with 2...

FDG-PET in immunocompetent patients with primary central nervous system lymphoma: correlation with MRI and clinical follow-up.

PurposeThe role of FDG-PET in primary central nervous system lymphoma (PCNSL) is unclear. It was the aim of this study to investigate the role of FDG-PET in detecting PCNSL and in predicting response to chemotherapy.MethodsAn FDG-PET scan of the brain was performed in 15 patients with histologically proven PCNSL (16 PET examinations, Siemens ECAT EXACT). PET was planned to investigate patients at the time of primary diagnosis, after chemotherapy and at the time of suspected relapse in seven, five and three cases, respectively. All except two patients simultaneously underwent MRI of the brain. FDG-PET results were correlated with histological results after stereotactic biopsy (primary diagnosis group) and with clinical data and MRI during follow-up.ResultsSix of the seven patients in the primary diagnosis group demonstrated a true positive finding (86%). In one of the true positive PET patients, there were two tumour lesions, one of which was only detectable on the FLAIR MRI sequence. In five patients, FDG-PET showed no sign of PCNSL during ongoing chemotherapy. These results were confirmed by the clinical follow-up (mean 26.6 months). MRI demonstrated minimal residual disease which had disappeared on further follow-up MRI in three of these five patients at the time of PET scanning. Recurrence of disease was confirmed concordantly by FDG-PET and MRI in three different patients. The standardised uptake value of all tumours was 10.2 (4.3–13.7).ConclusionPCNSLs demonstrate high FDG uptake and can be diagnosed by FDG-PET with high sensitivity. It seems that FDG-PET is suitable for early therapeutic monitoring after chemotherapy.

Mitral valve repair in patients with end stage cardiomyopathy: who benefits?

OBJECTIVE Patients with end stage cardiomyopathy frequently present with additional severe mitral regurgitation. We analyzed the outcome of mitral valve reconstruction in this high risk patient group. METHODS Sixty-six patients with significant mitral regurgitation and an ejection fraction (EF) below 30% (dilated cardiomyopathy=53, ischemic cardiomyopathy (ICM)=13) were retrospectively evaluated from 07/96 and 02/02. All received annuloplasty ring implantation and additional repair (n=4) if required. Mean follow-up was 28+/-18 months. RESULTS Mitral valve repair (MVR) was technically feasible in all patients. Intraoperative transesophageal echocardiography (TEE) revealed none (n=60) or only trivial (n=6) residual mitral regurgitation. Thirty day mortality was 6.1%. Actuarial survival after 1 and 5 years was 86+/-4 and 66+/-8%, respectively. During follow-up seven patients were transplanted due to lack of clinical improvement after 10+/-7 months (range 1-23). Echocardiography revealed a significant improvement in EF (25+/-10.5% pre-op, 34+/-15% post-op) and a slight decrease in left ventricular end-diastolic diameter (69+/-10 mm pre-op, 67+/-13 mm follow up). Patients were in NYHA functional -class 3 (median) preoperatively and in class 2 at long term-follow-up. Gender, left ventricular enddiastolic diameter, preoperative ejection fraction or type of surgical approach (sternotomy, right lateral minithoracotomy) had no significant influence on patient outcome. Patients with ICM or patients older than 60 years showed an increased risk for clinical events both early post-operatively and at long-term follow-up. CONCLUSION MVR can be performed with low perioperative morbidity and mortality even in patients with advanced heart failure, modifying selection criteria for potential candidates may further improve long term outcome.

Regression of Inflammation in Atherosclerosis by the LXR Agonist R211945 A Noninvasive Assessment and Comparison With Atorvastatin

OBJECTIVES The aim of this study was to noninvasively detect the anti-inflammatory properties of the novel liver X receptor agonist R211945. BACKGROUND R211945 induces reversal cholesterol transport and modulates inflammation in atherosclerotic plaques. We aimed to characterize with (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced cardiac magnetic resonance (DCE-CMR) inflammation and neovascularization, respectively, in atherosclerotic plaques with R211945 treatment compared with atorvastatin treatment and a control. METHODS Twenty-one atherosclerotic New Zealand white rabbits were divided into 3 groups (control, R211945 [3 mg/kg orally], and atorvastatin [3 mg/kg orally] groups). All groups underwent (18)F-FDG-PET/CT and DCE-CMR at baseline and at 1 and 3 months after treatment initiation. Concomitantly, serum metabolic parameters and histology were assessed. For statistical analysis, continuous DCE-CMR and PET/CT outcomes were modeled as linear functions of time by using a linear mixed model, whereas the histological data, animal characteristics data, and nonlinear regression imaging data were analyzed with a 2-tailed Student t test. RESULTS (18)F-FDG-PET/CT detected a decrease in mean and maximum standard uptake values (SUV) over time in the R211945 group (both p = 0.001), indicating inflammation regression. The atorvastatin group displayed no significant change (p = 0.371 and p = 0.600, respectively), indicating no progression or regression. The control group demonstrated an increase in SUV (p = 0.01 and p = 0.04, respectively), indicating progression. There was a significant interaction between time and group for mean and maximum SUV (p = 0.0003 and p = 0.0016, respectively) . DCE-CMR detected a trend toward difference (p = 0.06) in the area under the curve in the atorvastatin group, suggesting a decrease in neovascularization. There was no significant interaction between time and group (p = 0.6350 and p = 0.8011, respectively). Macrophage and apolipoprotein B immunoreactivity decreased in the R211945 and atorvastatin groups (p < 0.0001 and p = 0.0004, respectively), and R211945 decreased oxidized phospholipid immunoreactivity (p = 0.02). CONCLUSIONS Noninvasive imaging with (18)F-FDG-PET/CT and DCE-CMR and histological analysis demonstrated significant anti-inflammatory effects of the LXR agonist R211945 compared with atorvastatin. The results suggest a possible role for LXR agonists in the treatment of atherosclerosis.

Impact of noninsulin-dependent type 2 diabetes on carotid wall 18F-fluorodeoxyglucose positron emission tomography uptake.

OBJECTIVES In this study, the impact of noninsulin-dependent type 2 diabetes mellitus on carotid wall (18)F-fluorodeoxyglucose (FDG) uptake in patients with documented or suspected cardiovascular disease was evaluated. BACKGROUND Inflammation is a pivotal process in the progression of atherosclerosis, which can be noninvasively imaged by FDG positron emission tomography (FDG-PET). METHODS Carotid artery wall FDG uptake was quantified in 134 patients (age 60.2 ± 9.7 years; diabetic subjects, n = 43). The pre-scan glucose (gluc) level corrected mean of the maximum standardized uptake value (SUV) values ((mean)SUV(gluc)), mean of the maximum target-to-background ratio ((mean)TBR(gluc)), and single hottest segment (SHS(gluc)) of FDG uptake in the artery wall were calculated. Associations between FDG uptake, the presence of risk factors for atherosclerosis, and diabetes were then assessed by multiple regression analysis with backward elimination. RESULTS The study demonstrated a significant association between diabetes and FDG uptake in the arterial wall (diabetes (mean)SUV(gluc) β = 0.324, (mean)TBR(gluc) β = 0.317, and SHS(gluc) β = 0.298; for all, p < 0.0001). In addition, in diabetic patients, both body mass index ≥ 30 kg/m(2) ((mean)SUV(gluc) β = 0.4, (mean)TBR(gluc) β = 0.357, and SHS(gluc) β = 0.388; for all, p < 0.015) and smoking ((mean)TBR(gluc), β = 0.312; SHS(gluc), β = 0.324; for all, p < 0.04) were significantly associated with FDG uptake. CONCLUSIONS Type 2 diabetes was significantly associated with carotid wall FDG uptake in patients with known or suspected cardiovascular disease. In diabetic patients, obesity and smoking add to the risk of increased FDG uptake values.

Molecular imaging of brown adipose tissue in health and disease

PurposeBrown adipose tissue (BAT) has transformed from an interfering tissue in oncological 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily.MethodsThis review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated.ResultsProspective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, 18F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to 18F-FDG, other radiopharmaceuticals such as 99mTc-sestamibi, 123I-metaiodobenzylguanidine (MIBG), 18F-fluorodopa and 18F-14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation.ConclusionMolecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity.

Temporary Extracorporeal Membrane Oxygenation in Patients with Refractory Postoperative Cardiogenic Shock—A Single Center Experience

Abstract  Background: Approximately 1% of patients require temporary circulatory support due to refractory cardiogenic shock following cardiac surgery. Such patients are at very high risk for subsequent morbidity and mortality. We evaluated the results of temporary extracorporeal membrane oxygenation (ECMO) support in patients with postcardiotomy cardiogenic shock. Methods: From November 1997 to February 2000, 7900 patients underwent cardiac surgery in our institution. Ninety‐five patients (1.2%) (CABG, n = 63; AVR, n = 16; CABG and AVR, n = 8; other procedures, n = 8) required temporary postoperative ECMO support. ECMO implantation was performed via the femoral vessels or via the right atrium and ascending aorta. Intraaortic balloon counterpulsation was employed in all patients. Results: Mean duration of ECMO support was 2.8 ± 2.1 days. Forty‐five patients (47%) were successfully weaned from ECMO. Of these, 28 patients were discharged from hospital 35.8 ± 20.8 days post‐ECMO support. Overall hospital mortality for all ECMO patients was considerable at 71%. Mortality rate in the combined CABG and AVR group was 100% (P < 0.05 versus the other surgical groups). ECMO support was complicated by renal failure in 64% of patients, bleeding requiring mediastinal reexploration in 62%, ischemia of the lower limbs in 16%, cerebral edema in 6%, and cerebral hemorrhage in 3%. Conclusions: ECMO is a suitable technique for short‐term treatment of refractory postoperative low cardiac output. Mortality rates are comparable to other cardiac assist devices, with approximately 30% of patients able to be discharged from hospital. (J Card Surg 2003;18:512‐518)

The complementary roles of dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose PET/CT for imaging of carotid atherosclerosis

PurposeInflammation and neovascularization in vulnerable atherosclerotic plaques are key features for severe clinical events. Dynamic contrast-enhanced (DCE) MRI and FDG PET are two noninvasive imaging techniques capable of quantifying plaque neovascularization and inflammatory infiltrate, respectively. However, their mutual role in defining plaque vulnerability and their possible overlap has not been thoroughly investigated. We studied the relationship between DCE-MRI and 18F-FDG PET data from the carotid arteries of 40 subjects with coronary heart disease (CHD) or CHD risk equivalent, as a substudy of the dal-PLAQUE trial (NCT00655473).MethodsThe dal-PLAQUE trial was a multicenter study that evaluated dalcetrapib, a cholesteryl ester transfer protein modulator. Subjects underwent anatomical MRI, DCE-MRI and 18F-FDG PET. Only baseline imaging and biomarker data (before randomization) from dal-PLAQUE were used as part of this substudy. Our primary goal was to evaluate the relationship between DCE-MRI and 18F-FDG PET data. As secondary endpoints, we evaluated the relationship between (a) PET data and whole-vessel anatomical MRI data, and (b) DCE-MRI and matching anatomical MRI data. All correlations were estimated using a mixed linear model.ResultsWe found a significant inverse relationship between several perfusion indices by DCE-MRI and 18F-FDG uptake by PET. Regarding our secondary endpoints, there was a significant relationship between plaque burden measured by anatomical MRI with several perfusion indices by DCE-MRI and 18F-FDG uptake by PET. No relationship was found between plaque composition by anatomical MRI and DCE-MRI or 18F-FDG PET metrics.ConclusionIn this study we observed a significant, weak inverse relationship between inflammation measured as 18F-FDG uptake by PET and plaque perfusion by DCE-MRI. Our findings suggest that there may be a complex relationship between plaque inflammation and microvascularization during the different stages of plaque development. 18F-FDG PET and DCE-MRI may have complementary roles in future clinical practice in identifying subjects at high risk of cardiovascular events.

Palliation and Survival After Repeated 188 Re-HEDP Therapy of Hormone-Refractory Bone Metastases of Prostate Cancer: A Retrospective Analysis

This retrospective study compared the effects of single and multiple administrations of 186Re-hydroxyethylidenediphosphonate (186Re-HEDP) on palliation and survival of prostate cancer patients presenting with more than 5 skeletal metastases. Methods: A total of 60 patients were divided into 3 groups. Group A (n = 19) consisted of patients who had received a single injection; group B (n = 19), patients who had 2 injections; and group C (n = 22), patients who had 3 or more successive injections. The 188Re-HEDP was prepared using non–carrier-added 188Re obtained from an in-house 188W/188Re generator after dilution with carrier perrhenate. Patients’ data available from the referring physicians—including prostate-specific antigen levels—were entered into a Windows-based matrix and analyzed using a statistical program. The Gleason scores were similar for all 3 groups. Results: Mean survival from the start of treatment was 4.50 ± 0.81 mo (95% confidence interval [CI], 2.92–6.08) for group A, 9.98 ± 2.21 mo (95% CI, 5.65–14.31) for group B, and 15.66 ± 3.23 (95% CI, 9.33–22.0) for group C. Although the 3 groups did not differ in Gleason score, the number of lost life-years was significantly lower in group C than in groups A and B. Pain palliation was achieved in 89.5% of group A, 94.7% of group B, and 90.9% of group C. Conclusion: Posttreatment overall survival could be improved from 4.50 to 15.66 mo by multiple-injection bone-targeted therapy with 188Re-HEDP, when compared with a single injection. Significant pain palliation was common and independent of administration frequency.

Combined 18F-FDG PET-CT and DCE-MRI to Assess Inflammation and Microvascularization in Atherosclerotic Plaques

Background and Purpose— Hallmarks of vulnerable atherosclerotic plaques are inflammation that can be assessed with 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography, and increased neovascularization that can be evaluated by dynamic contrast–enhanced-MRI. It remains unclear whether these parameters are correlated or represent independent imaging parameters. This study determines whether there is a correlation between inflammation and neovascularization in atherosclerotic carotid plaques. Methods— A total of 58 patients with transient ischemic attack or minor stroke in the carotid territory and ipsilateral carotid artery stenosis of 30% to 69% were included. All patients underwent positron emission tomography/computed tomography and dynamic contrast–enhanced-MRI of the carotid plaque. 18Fluorine-fluorodeoxyglucose standard uptake values with target/background ratio were determined. Neovascularization was quantified by the mean (leakage) volume transfer constant Ktrans. Spearman rank correlation coefficients between target/background ratio and Ktrans were calculated. Results— Images suitable for further analysis were obtained in 49 patients. A weak but significant positive correlation between target/background ratio and mean Ktrans (Spearman &rgr;=0.30 [P=0.035]) and 75th percentile Ktrans (Spearman &rgr;=0.29 [P=0.041]) was found. Conclusions— There is a weak but significant positive correlation between inflammation on positron emission tomography/computed tomography and neovascularization as assessed with dynamic contrast–enhanced-MRI. Future studies should investigate which imaging modality has the highest predictive value for recurrent stroke, as these are not interchangeable. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00451529.