Harald Schicha

Comparison of Low-Dose Dobutamine–Gradient-Echo Magnetic Resonance Imaging and Positron Emission Tomography With [18F]Fluorodeoxyglucose in Patients With Chronic Coronary Artery Disease A Functional and Morphological Approach to the Detection of Residual Myocardial Viability

BACKGROUND There have been conflicting reports of whether substantial myocardial thinning alone as an indirect sign of myocardial scarring is sufficient evidence to exclude the presence of viable myocardium in patients with previous myocardial infarction and persisting regional left ventricular akinesia. Demonstration of a dobutamine-induced contraction reserve in postischemic viable but akinetic myocardium may serve as a direct indicator of myocardial viability. In the present study, end-diastolic wall thickness at rest and dobutamine-induced systolic wall thickening assessed by magnetic resonance imaging (MRI) were compared with corresponding [18F]fluorodeoxyglucose uptake as assessed by positron emission tomography (FDG-PET). METHODS AND RESULTS Thirty-five patients with myocardial infarction (infarct age, > 4 months) and regional akinesia or dyskinesia assessed by left ventriculography underwent rest and dobutamine MRI studies (10 micrograms dobutamine.min-1.kg-1) and FDG-PET followed by segmental analyses of end-diastolic wall thickness, systolic wall thickening, and FDG uptake in corresponding short-axis tomograms. Two definitions of viability, as assessed by MRI, of a segment akinetic at baseline were used: (1) end-diastolic wall thickness of > or = 5.5 mm (the mean minus 2.5 SD of a healthy control group [n = 21]) and (2) evidence of dobutamine-induced systolic wall thickening > or = 1 mm. Segments were graded as viable by FDG-PET if FDG uptake was > or = 50% of the maximum uptake in a region with normal wall motion as assessed by left ventriculography. Preserved end-diastolic wall thickness in akinetic regions was found in 17 of 35 (48%) patients at rest, and functional recovery within the infarct region was found in 19 of 35 (54%) patients during dobutamine infusion. Viability of the infarct region was indicated by FDG-PET in 23 of 35 patients (66%), yielding a diagnostic agreement between FDG uptake and myocardial morphology in 29 of 35 (83%) and between dobutamine-induced contraction reserve and FDG-PET in 31 of 35 (89%). Of 2200 segments, 482 (22%) were akinetic at rest. Of these akinetic segments, 234 (48%) had preserved end-diastolic wall thickness, 251 (52%) had a dobutamine-induced contraction reserve, and 299 (62%) were graded as viable by FDG-PET. Correlations of FDG uptake with end-diastolic wall thickness at rest (r = .48) and with dobutamine-induced wall thickening (r = .42) were similar. Comparison of segmental MRI and FDG-PET gradings indicated that dobutamine-induced wall thickening was a better predictor of residual metabolic activity (sensitivity, 81%; specificity, 95%; positive predictive accuracy, 96% than was end-diastolic wall thickness (sensitivity, 72%; specificity, 89%; positive predictive accuracy, 91%). However, grading a segment as viable if at least one of both MRI parameters fulfilled viability criteria improved the sensitivity (88%) of MRI for FDG-PET-assessed metabolic activity without a major decrease in specificity (87%) or positive predictive accuracy (92%). CONCLUSIONS Viable myocardium is characterized by preserved end-diastolic wall thickness and a dobutamine-inducible contraction reserve. Both parameters should be taken into account to maximize the sensitivity of MRI in the detection of regions with signs of viability on FDG-PET images.

Dobutamine Magnetic Resonance Imaging Predicts Contractile Recovery of Chronically Dysfunctional Myocardium After Successful Revascularization

OBJECTIVES This study sought to evaluate whether myocardial viability, as assessed by magnetic resonance imaging (MRI), reliably predicts postrevascularization left ventricular (LV) recovery. BACKGROUND Compared with positron emission tomographic findings, MRI has proved to be a reliable technique for the identification of residual myocardial viability. However, the predictive accuracy of MRI-assessed preserved end-diastolic wall thickness (DWT) and dobutamine-induced systolic wall thickening (SWT) for LV functional recovery has not yet been evaluated. METHODS Rest and low dose dobutamine MRI was performed in 43 patients with a chronic infarct (> or =4 months since ischemic event) and LV dysfunction who had undergone revascularization of the infarct-related vessel. On the basis of segmental evaluation of corresponding short-axis tomograms, infarct regions were graded viable by MRI if 1) DWT was > or =5.5 mm, and 2) dobutamine-induced SWT was > or =2 mm in > or =50% of dysfunctional segments related to the infarct region. Functional recovery was defined as SWT > or =2 mm in > or =50% of infarct-related segments at rest 4 to 6 months after successful revascularization. RESULTS Recovery of regional SWT could be observed in 27 (63%) of 43 patients. Comparison MRI grading before and after revascularization indicated that dobutamine-induced SWT was a better predictor of LV functional recovery (sensitivity 89%, specificity 94%) than was preserved DWT (sensitivity 92%, specificity 56%). Segments that remained akinetic after revascularization had significantly lower DWT (6.0+/-3.1 mm [n = 219] vs. 9.8+/-2.6 mm [n = 188], p < 0.001) than those with improved SWT. Left ventricular ejection fraction increased significantly in patients with dobutamine-induced SWT than in those with no contractile reserve (14+/-9% vs. 3+/-9%, p < 0.0002), and the magnitude of this increase was correlated with the number of dobutamine-responsive segments per infarct region (r = 0.68, p < 0.0001). CONCLUSIONS Quantitative assessment of dobutamine-induced SWT in chronic infarcts by MRI is a highly accurate predictor of LV functional recovery, and the presence of significantly reduced DWT reliably indicates irreversible myocardial damage. Therefore, dobutamine stress testing for the assessment of myocardial viability can be restricted to patients with preserved DWT.

Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma

In the HD15 trial of the German Hodgkin Study Group, the negative predictive value (NPV) of positron emission tomography (PET) using [(18)F]-fluorodeoxyglucose in advanced-stage Hodgkin lymphoma (HL) was evaluated. A total of 817 patients were enrolled and randomly assigned to receive BEACOPP-based chemotherapy. After completion of chemotherapy, residual disease measuring more than or equal to 2.5 cm in diameter was assessed by PET in 311 patients. The NPV of PET was defined as the proportion of PET(-) patients without progression, relapse, or irradiation within 12 months after PET review panel. The progression-free survival was 96% for PET(-) patients (95% confidence interval [CI], 94%-99%) and 86% for PET(+) patients (95% CI, 78%-95%, P = .011). The NPV for PET in this analysis was 94% (95% CI, 91%-97%). Thus, consolidation radiotherapy can be omitted in PET(-) patients with residual disease without increasing the risk for progression or early relapse compared with patients in complete remission. The impact of this finding on the overall survival at 5 years must be awaited. Until then, response adapted therapy guided by PET for HL patients seems to be a promising approach that should be further evaluated in clinical trials. This trial is registered at http://isrctn.org study as #ISRCTN32443041.

Fluorine-18 fluorodeoxyglucose positron emission tomography and iodine-131 whole-body scintigraphy in the follow-up of differentiated thyroid cancer

Abstract.Metastases of differentiated thyroid cancer may show different uptake patterns for fluorine-18 fluorodeoxyglucose and [131I]NaI. FDG positron emission tomography (PET), iodine-131 whole-body scintigraphy (131I WBS) and magnetic resonance imaging were performed in 58 unselected patients, and spiral computed tomography (CT) of the lung in 25 patients. Thirty-eight patients presented with papillary carcinomas, 15 patients with follicular carcinomas and five patients with variants of follicular carcinoma. Primary tumour stage (pT) was pT1 in 3, pT2 in 19, pT3 in 11 and pT4 in 25 cases. For the detection of metastases, FDG PET was found to have a sensitivity of 50%, 131I WBS a sensitivity of 61%, and the two methods combined a sensitivity of 86%. When FDG PET was limited to patients with elevated thyroglobulin (Tg) levels and negative 131I WBS, the sensitivity of this algorithm was 82%. Of the 21 patients with lymph node metastases, seven presented with FDG uptake but no iodine uptake. In four of them, a second FDG hot spot appeared in a lymph node metastasis of normal size. Five of the seven patients underwent surgery. None of the eight patients with pulmonary metastases smaller than 1 cm exhibited FDG uptake, while five of them had iodine uptake. All had positive results on spiral CT. In conclusion, FDG PET cannot be substituted for 131I WBS. If the Tg level is elevated and 131I WBS is negative, FDG PET can be used to detect lymph node metastases and complements anatomical imaging. A spiral CT of the lung is useful to exclude pulmonary metastases before planning a dissection of iodine-negative lymph node metastases.

2[18F]-fluoro-2-deoxy-D-glucose positron emission tomography is a sensitive tool for the detection of occult primary cancer (carcinoma of unknown primary syndrome) with head and neck lymph node manifestation

BACKGROUND: The neck lymph nodes are a common site of metastases from carcinoma of unknown primary (CUP syndrome). 2[ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET) has been shown to be a sensitive tool for detecting primary malignant lesions as well as metastatic spread. We have prospectively investigated the sensitivity of 18-FDG-PET in detecting occult primary carcinomas with manifestation in the head and neck lymph nodes. METHODS: From May 1994 to July 1998, in 723 patients a cancer of the head and neck was diagnosed at the University of Cologne ENT outpatient clinic. The routinely performed staging procedures were chest radiography; full blood count; cervical and liver ultrasound; endoscopy of the nasopharynx, oropharynx, hypopharynx, larynx, and esophagus; and laboratory analyses. After the staging workup, in 27 of 723 patients (3.7%) CUP syndrome had to be presumed because the primary cancer could not be detected. In these patients 18-FDG-PET was performed, and images were reconstructed with a transmission-emission fusion technique. RESULTS: In 7 of 27 patients (26%) 18-FDG-PET revealed an unknown primary: in 2 a bronchial carcinoma, in 2 a nasopharyngeal carcinoma, in 1 a squamous cell carcinoma of the parotid gland, in 1 a squamous cell carcinoma of the hypopharynx, and in 1 a carcinoma of the tonsil. In 4 of 7 patients the occult primary tumor was removed surgically. In 8 of 27 patients therapeutic strategy was changed as a result of the 18-FDG-PET findings. CONCLUSION: 18-FDG-PET should be performed in all patients with CUP syndrome after conventional diagnostic workup fails to identify the primary.

Cost-effectiveness of FDG-PET for the management of potentially operable non-small cell lung cancer: priority for a PET-based strategy after nodal-negative CT results

Abstract. Decision analysis is used here to establish the most cost-effective strategy for management of potentially operable non-small cell lung cancers (NSCLCs). The strategies compared were conventional staging (strategy A), dedicated systems of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) in patients with normal-sized (strategy B) or in patients with enlarged mediastinal lymph nodes (part of strategy C), and FDG-PET followed by exclusion from surgical procedures when both computed tomography (CT) and PET were positive for mediastinal lymph nodes (strategy D) or when PET alone was positive (strategy E). Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes, and at 0.95 and 0.76 when these lymph nodes were enlarged. The calculated probability of up-staging to M1 by using PET was 0.05. The costs quoted correspond to the cost reimbursed in 1999 by the public health provider in Germany. The incremental cost-effectiveness ratio (ICER) of strategy B was much more favourable (143 EUR/LYS; LYS = life year saved) than the ICER of strategy C (36,667 EUR/LYS). In strategy B, the use of PET did not raise the overall costs because the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. The exclusion from biopsy confirmation in strategies D and E led to cost savings that did not justify the expected reduction in life expectancy. In sensitivity analyses, the ICERs of strategy B were robust to the pretest likelihood of N2/N3, to penalized test parameters of PET and to reimbursement of PET. However, the ICER of strategy B would be raised to 28,000 EUR/LYS through use of thoracic PET without whole-body scanning. To conclude, the implementation of whole-body PET with a full ring of detectors in the preoperative staging of patients with NSCLC and normal-sized lymph nodes is clearly cost-effective. However, patients with nodal-positive PET results should not be excluded from biopsy.

Qualitative [18F]FDG positron emission tomography in primary breast cancer: clinical relevance and practicability

Positron emission tomography (PET) using fluorine-18 2-deoxy-2-fluoro-d-glucose (FDG) is of potential value for the diagnosis of malignant tumours. The aim of this study was to evaluate the use of FDG PET in patients with breast tumours, appraising its applicability in visualising primary carcinomas and regional metastases in a clinical setting. Results of FDG PET were compared with those of mammography, breast ultrasonography and histology in 30 patients with inconclusive breast findings. For PET, transmission and emission images were taken in one or two scan positions, depending on the available time and the clinical status of patients. PET showed focal FDG uptake with high contrast in 21 of 23 primary carcinomas. In one patient, only PET correctly visualized multifocal disease (three foci, Ø 0.4–1 cm). The accuracy of PET in the detection of primary breast cancer was 90%, and in the detection of involved axillary lymph nodes, 94%. All metastases (lymph nodes, lungs, bones, soft tissues) covered by the field of view and demonstrated by other methods (X-ray, computed tomography, magnetic resonance imaging, bone scan) showed FDG uptake. In three patients, only PET initiated further diagnostic procedures. The results indicate that FDG PET can provide a rapid diagnostic study (45–60 min) and allows accurate tumour staging of several organ systems for primary tumour and metastases with a single imaging study in a routine clinical setting.

Predictive value of low dose dobutamine transesophageal echocardiography and fluorine-18 fluorodeoxyglucose positron emission tomography for recovery of regional left ventricular function after successful revascularization☆

OBJECTIVES This study was designed to assess the predictive value of myocardial viability diagnosed by dobutamine transesophageal echocardiography and fluorine (F)-18 fluorodeoxyglucose positron emission tomography for left ventricular functional recovery after revascularization in patients with chronic left ventricular dysfunction. BACKGROUND The identification of akinetic but viable myocardium is of particular importance for the selection of patients with a compromised left ventricle who will benefit from coronary revascularization. METHODS Multiplane rest and dobutamine transesophageal echocardiography (dobutamine, 5 and 10 microg/min per kg) studies and F-18 fluorodeoxyglucose positron emission tomographic studies at rest were performed in 2 patients with 1) previous myocardial infarction and regional akinesia, 2) a stenosed infarct-related coronary artery, and 3) a patent infarct-related vessel after revascularization. A basally akinetic segment was considered viable by transesophageal echocardiography if dobutamine-induced contractile reserve could be observed. Viability by positron emission tomography was defined as F-18 fluorodeoxyglucose uptake > or = 50% of the maximal uptake in a region with normal wall motion. Recovery of regional left ventricular function 4 to 6 months after revascularization was diagnosed by transesophageal echocardiography if > or = 50% of segments akinetic at baseline had improved wall thickening. RESULTS Dobutamine transesophageal echocardiography identified viable infarct regions in 25 (59%) of 42 patients, and F-18 fluorodeoxyglucose positron emission tomography in 30 (71%) of 42 patients, yielding diagnostic agreement in 86% of patients. Sensitivity and specificity for prediction of left ventricular functional recovery in individual patients was 92% and 88%, respectively, for dobutamine transesophageal echocardiography versus 96% and 69% for F-18 fluorodeoxyglucose positron emission tomography. Segments remaining akinetic after revascularization had a significantly lower (p < 0.001) F-18 fluorodeoxyglucose uptake (48 +/- 15%) than that (73 +/- 15%) of segments with recovery of regional left ventricular function. CONCLUSIONS Both dobutamine transesophageal echocardiography and F-18 fluorodeoxyglucose positron emission tomography were highly sensitive in predicting functional recovery of chronically kinetic or dyskinetic myocardium after successful revascularization. Thus, dobutamine transesophageal echocardiography is a clinically valuable alternative to F-18 fluorodeoxyglucose positron emission tomography for assessing residual viability and predicting functional recovery after revascularization.

Whole-body positron emission tomography using 18F-fluorodeoxyglucose for initial staging of patients with Hodgkin's disease

Abstract. An accurate initial staging of patients with Hodgkins disease (HD) is important for the evaluation of clinical stage and risk factors, which are crucial for the choice of an appropriate treatment. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful for detecting active tumor tissue in patients with lymphoproliferative diseases and may contribute to conventional staging methods in patients with HD. Twenty-two patients who presented with newly diagnosed HD underwent conventional staging methods including computed tomography (CT) as well as FDG PET. Lesions apparent in FDG PET and CT were correlated to each other. Seventy-seven lesions were observed either in PET or CT or in both. In 48 (62%) lesions PET and CT were both positive. In 20 (26%) sites, PET was positive and CT negative. Of 22 patients (18%) 4 were upstaged due to these positive PET findings, and as a result one patient received a different therapeutic regimen. PET failed to detect nine (12%) CT-positive sites in six patients. Statistically, these data are reflected by a sensitivity for PET and CT of 88% and 74%, respectively. Specificity of both imaging modalities was 100%. PET can contribute valuable information as an additional staging examination and led to an upstaging in some patients with primary HD. However, PET should not be used as the only imaging modality as it failed to detect CT-positive, active tumor regions in some cases.

Assessment of viable myocardium by dobutamine transesophageal echocardiography and comparison with fluorine-18 fluorodeoxyglucose positron emission tomography☆

OBJECTIVES The aim of this study was to assess whether dobutamine transesophageal echocardiography can identify viable myocardium in patients with chronic myocardial infarction. BACKGROUND Experimental and clinical studies have shown that dobutamine can recruit a contraction reserve in postischemic viable but akinetic segments, indicating that dobutamine-induced functional recovery is a potential ultrasound marker of myocardial viability. METHODS Forty patients underwent rest and dobutamine transesophageal echocardiography (dobutamine 5, 10 and 20 micrograms/kg body weight per min) and fluorine-18 (F-18) fluorodeoxyglucose positron emission tomography at rest. Three representative short-axis tomograms and a transverse four-chamber-view were used for wall motion and F-18 fluorodeoxyglucose-uptake analysis in corresponding myocardial regions. A basally asynergic segment was considered viable by transesophageal echocardiography if dobutamine-induced systolic wall motion could be observed. Viability by positron emission tomography was defined as F-18 fluorodeoxyglucose uptake > or = 50% of the maximal uptake in a region with normal wall motion by left ventriculography. RESULTS Functional recovery within the infarct region was found in 21 (53%) of 40 patients during dobutamine infusion. Infarct region-related viability by F-18 fluorodeoxyglucose uptake was diagnosed in 25 (63%) of 40 patients, yielding a diagnostic agreement between both techniques in 90% of patients. In 210 (89%) of 235 akinetic segments at rest, data on myocardial viability were concordant by the two techniques. The positive and negative predictive accuracy of dobutamine transesophageal echocardiography for viability defined by F-18 fluorodeoxyglucose uptake was 81% and 97%, respectively. Such uptake was significantly different (p < 0.001) between segments remaining akinetic (mean +/- SD 45 +/- 9%) during dobutamine infusion and segments with a dobutamine-induced contraction reserve (68 +/- 11%). CONCLUSIONS Dobutamine transesophageal echocardiography provides a promising low cost and widely available approach to unmask myocardial viability in patients with chronic myocardial infarction, and results compare favorably with those of F-18 fluorodeoxyglucose positron emission tomography.