Sibylle Ziegler

Delayed Response of Myocardial Flow Reserve to Lipid-Lowering Therapy With Fluvastatin

BACKGROUND Lipid-lowering therapy can improve endothelial function in patients with coronary artery disease (CAD) and hypercholesterolemia. Little is known about induced changes in myocardial microcirculation. This study prospectively investigated the temporal effects of lipid-lowering therapy with fluvastatin on coronary flow and flow reserve (CFR) in patients with CAD assessed by PET. METHODS AND RESULTS In an open clinical trial, CFR was studied in 15 patients with angiographically documented multivessel CAD and hypercholesterolemia (LDL >160 mg/dL). Dynamic 13N-labeled ammonia PET imaging in conjunction with adenosine was used to assess regional and global CFR at baseline as well as at 2 and 6 months during treatment with fluvastatin (60 to 80 mg/d). Despite a rapid decrease in total cholesterol (29+/-6%) and LDL (37+/-9%), myocardial blood flow at rest and during stress was unchanged after 2 months of treatment (2.7+/-0.9 versus 2.5+/-0.6 mL x g-1 x min-1). At 6 months, stress blood flow as well as CFR increased significantly (3.4+/-1.0 mL x g-1 x min-1). No change in hemodynamic parameters was noted during the entire study. Nine of 15 patients increased CFR by >20%. All responders demonstrated improvement in anginal symptoms, whereas nonresponders stated no change (n=4) or worsening of symptoms (n=2). The improvement in CFR was not related to the amount of lipid lowering and was independent of the severity of stenoses. CONCLUSIONS Improvement in stress blood flow and CFR is delayed compared with the lipid-lowering effect of fluvastatin, suggesting a slow recovery of the vasodilatory response to adenosine.

Evaluation of the attenuation properties of MR equipment for its use in a whole-body PET/MR scanner

The combination of magnetic resonance imaging (MR) and positron emission tomography (PET) scanners can provide a powerful tool for clinical diagnosis and investigation. Among the challenges of developing a combined scanner, obtaining attenuation maps for PET reconstruction is of critical importance. This requires accounting for the presence of MR hardware in the field of view. The attenuation introduced by this hardware cannot be obtained from MR data. We propose the creation of attenuation models of MR hardware, to be registered into the MR-based attenuation map prior to PET reconstruction. Two steps were followed to assess the viability of this method. First, transmission and emission measurements were performed on MR components (RF coils and medical probes). The severity of the artifacts in the reconstructed PET images was evaluated. Secondly, a high-exposure computed tomography (CT) scan was used to obtain a model of a head coil. This model was registered into the attenuation map of PET/CT scans of a uniform phantom fitted with the coil. The resulting PET images were compared to the PET/CT reconstruction in the absence of coils. The artifacts introduced by misregistration of the model were studied. The transmission scans revealed 17% count loss due to the presence of head and neck coils in the field of view. Important sources of attenuation were found in the lock, signal cables and connectors. However, the worst source of attenuation was the casing between both coils. None of the measured medical probes introduced a significant amount of attenuation. Concerning the attenuation model of the head coil, reconstructed PET images with model-based correction were comparable to the reference PET/CT reconstruction. However, inaccuracies greater than 1-2 mm in the axial positioning of the model led to important artifacts. In conclusion, the results show that model-based attenuation correction is possible. Using a high-exposure scan to create an attenuation model of the coils has been proved feasible. However, adequate registration of the model is mandatory.

Inter-crystal scatter in a dual layer, high resolution LSO-APD positron emission tomograph.

Improving system efficiency without jeopardizing spatial resolution is one of the main problems of small animal PET scanners. In pursuit of this goal, the future LSO-APD-PET prototype MADPET-II will combine highly granulated detector modules with a dual layer structure. The individual readout of the LSO crystals allows separately handling multiple signals related to those photons scattering between different crystal units (inter-crystal scatter, ICS). The contribution of ICS events can significantly increase the system efficiency. Such coincidences are not characterized by a unique LOR. However, in order to minimize resolution degradation, it would be desirable to identify the primary path of the ICS events. Since ICS is geometry dependent, this work was aimed at investigating the effects of ICS in the performance of the dual layer prototype. Different recovery algorithms to select the primary crystal were implemented and developed, and applied to Monte Carlo simulated data. Some of these algorithms were based on the properties of Compton kinematics. For a centred point source and a 100 keV lower energy threshold, the absolute system efficiency was found to increase by 35% when including ICS events: from 1.8% without ICS events to 2.8% with ICS. Similarly, for a threshold of 200 keV, the contribution of ICS coincidences still represented approximately 20% of the total detected coincidences, leading to an absolute system efficiency of almost 2%. The mispositioning introduced by processing ICS coincidences only led to a moderate broadening of the axial line spread function (LSF), especially at the tails of the profile (FWTM). This effect was also noticeable in the transaxial plane. In presence of scattering media (water-filled cylinder), the resolution degradation was dominated by the contribution of object scatter. The reconstructed images from a simulated homogeneous cylinder filled with activity with a non-active rod at its centre were employed to estimate the impact of ICS on the image quality. In general, the use of ICS coincidences increased the signal-to-noise ratio (SNR) but worsened contrast. The effects of ICS on resolution could be reduced by employing a new identification scheme based on the maximum signal and the Compton kinematics. This method yielded the highest identification rate for the correct photon trajectory, even for a finite energy resolution of 15% (511 keV). This technique also increased the SNR by 17% to 30% and preserved the image contrast. In conclusion, by combining individual crystal readout, a low energy threshold and an appropriate recovery scheme, the processing of ICS coincidences significantly increases the system efficiency without any substantial deterioration of the image quality.

Clinical Determinants of Ventricular Sympathetic Reinnervation After Orthotopic Heart Transplantation

Background—It has been demonstrated that ventricular sympathetic reinnervation after cardiac transplantation improves exercise performance. The extent of reinnervation increases with time but is variable. Little is known about other influencing factors. Methods and Results—Seventy-seven nonrejecting transplant recipients were cross-sectionally studied by PET with the catecholamine analogue C-11 hydroxyephedrine at 4.8±3.5 years after transplantation. Results were compared with history-derived parameters related to recipient’s clinical course before, during, and after surgery; donor characteristics; and immunogenetics. Partial reinnervation was observed in 52 patients (extent, 21±16% of left ventricle). Complete denervation was found in 25 patients at various times after transplantation. Reinnervation extent correlated with time after surgery (r =0.387;P <0.001) but also inversely with donor age (r =−0.309, P =0.006) and recipient age (r =−0.243, P =0.032). Maximal hydroxyephedrine retention correlated inversely with frequency of rejection episodes (r =−0.267, P =0.019), was reduced when aortic complications occurred perioperatively (9 patients), and correlated inversely with aortic cross-clamp time (r =−0.331, P =0.006). Other parameters were not associated with reinnervation. Patients were surveyed for clinical complications over >12 months after PET (until 7.3±4.2 years after transplantation), but significant effects of reinnervation on outcome were not observed. Conclusions—The present data suggest that sympathetic reinnervation after cardiac transplantation is not simply a function of time. Reinnervation is more likely with young age, fast and uncomplicated surgery, and low rejection frequency. Despite few effects on prognosis in otherwise healthy recipients, improved understanding of clinical determinants may contribute to enhance allograft reinnervation and thereby augment exercise capacity in the future.

Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries

OBJECTIVES Myocardial blood flow (MBF) in children late after arterial switch operation (ASO) was investigated quantitatively by positron emission tomography (PET). BACKGROUND In children with transposition of the great arteries (TGA), ASO is widely accepted as the management of choice. The long-term patency of coronary arteries after surgical transfer to the neo-aorta, however, remains a concern. METHODS Twenty-two normally developed, symptom-free children were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilation 10+/-1 years after ASO. A subgroup of 15 children (9+/-1 years; group A) had simple TGA and underwent ASO within 20 days after birth while 7 (13+/-3 years; group B) had complex TGA and underwent ASO and correction of associated anomalies later after birth. Ten young, healthy adults (26+/-6 years) served as the control group. RESULTS Resting MBF was not different between groups. After correction for the rate-pressure product as an index of cardiac work, younger children of group A had significantly higher MBF at rest compared to healthy adults (102+/-29 vs. 77+/-6 ml/100 g/min; p = 0.012) while flow in group B was not different from the other groups (85+/-22 ml/100 g/min; p = NS). Hyperemic blood flows were significantly lower in both groups after ASO compared to normals (290+/-42 ml/100 g/min for group A, 240+/-28 for group B, 340+/-57 for normals; p < 0.01); thus, coronary flow reserve was significantly lower in both groups after ASO compared to healthy adults (3.0+/-0.6 for group A, 2.9+/-0.6 for group B, 4.6+/-0.9 for normals; p < 0.01). CONCLUSIONS Blood flow measurements suggest decreased coronary reserve in the absence of ischemic symptoms in children late after arterial switch repair of TGA. The global impairment of stress flow dynamics may indicate altered vasoreactivity; however, the prognostic significance of these findings needs to be determined.

Textural Parameters of Tumor Heterogeneity in 18F-FDG PET/CT for Therapy Response Assessment and Prognosis in Patients with Locally Advanced Rectal Cancer

18F-FDG PET/CT is effective in the assessment of therapy response. Changes in glucose uptake or tumor size are used as a measure. Tumor heterogeneity was found to be a promising predictive and prognostic factor. We investigated textural parameters for their predictive and prognostic capability in patients with rectal cancer using histopathology as the gold standard. In addition, a comparison to clinical outcome was performed. Methods: Twenty-seven patients with rectal cancer underwent 18F-FDG PET/CT before, 2 wk after the start, and 4 wk after the completion of neoadjuvant chemoradiotherapy. In all PET/CT scans, conventional parameters (tumor volume, diameter, maximum and mean standardized uptake values, and total lesion glycolysis [TLG]) and textural parameters (coefficient of variation [COV], skewness, and kurtosis) were determined to assess tumor heterogeneity. Values on pretherapeutic PET/CT as well as changes early in the course of therapy and after therapy were compared with histopathologic response. In addition, the prognostic value was assessed by correlation with time to progression and survival time. Results: The COV showed a statistically significant capability to assess histopathologic response early in therapy (sensitivity, 68%; specificity, 88%) and after therapy (79% and 88%, respectively). Thereby, the COV had a higher area under the curve in receiver-operating-characteristic analysis than did any analyzed conventional parameter for early and late response assessment. The COV showed a statistically significant capability to evaluate disease progression and to predict survival, although the latter was not statistically significant. Conclusion: Tumor heterogeneity assessed by the COV, being superior to the investigated conventional parameters, is an important predictive factor in patients with rectal cancer. Furthermore, it can provide prognostic information. Therefore, its application is an important step for personalized treatment of rectal cancer.

Attenuation-corrected 99mTc-tetrofosmin single-photon emission computed tomography in the detection of viable myocardium: comparison with positron emission tomography using 18F-fluorodeoxyglucose

OBJECTIVES The purpose of this study was to assess the efficacy of attenuation-corrected (AC) technetium-99m (99mTc)-tetrofosmin single-photon emission computed tomography (SPECT) in detecting viable myocardium compared to 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND The role of 99mTc-labeled perfusion tracers in the assessment of myocardial viability remains controversial. Attenuation artifacts affect the diagnostic accuracy of SPECT images. METHODS Twenty-four patients with coronary artery disease (mean left ventricular ejection fraction 30%) underwent resting 99mTc-tetrofosmin SPECT and FDG PET imaging. Both AC and non-attenuation-corrected (NC) SPECT images were generated. RESULTS Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG on the patient basis increased from 79.8%+/-14.0% (mean+/-SD) on the NC images to 90.8%+/-10.6% on the AC images (p=0.002). The percentage of 99mTc-tetrofosmin defect segments within PET-viable segments, an estimate for the degree of underestimation of viability, decreased from 19.8%+/-15.2% on the NC images to 9.7%+/-12.6% on the AC images (p=0.01). Similar results were obtained when a 60% threshold was used to define viability by FDG PET. When the anterior-lateral and inferior-septal regions were separately analyzed, the effect of attenuation correction was significant only in the inferior-septal region. CONCLUSIONS The results indicate that AC 99mTc-tetrofosmin SPECT improves the detection of viable myocardium mainly by decreasing the underestimation of viability particularly in the inferior-septal region, although some underestimation/overestimation of viability may still occur even with attenuation correction.

Informatics and medicine. From molecules to populations.

OBJECTIVES To clarify challenges and research topics for informatics in health and to describe new approaches for interdisciplinary collaboration and education. METHODS Research challenges and possible solutions were elaborated by scientists of two universities using an interdisciplinary approach, in a series of meetings over several months. RESULTS AND CONCLUSION In order to translate scientific results from bench to bedside and further into an evidence-based and efficient health system, intensive collaboration is needed between experts from medicine, biology, informatics, engineering, public health, as well as social and economic sciences. Research challenges can be attributed to four areas: bioinformatics and systems biology, biomedical engineering and informatics, health informatics and individual healthcare, and public health informatics. In order to bridge existing gaps between different disciplines and cultures, we suggest focusing on interdisciplinary education, taking an integrative approach and starting interdisciplinary practice at early stages of education.

PET/MR in prostate cancer: technical aspects and potential diagnostic value.

PET/MR is a new multimodal imaging technique that is expected to improve diagnostic performance of imaging in conditions in which assessment of changes in soft tissue is important such as prostate cancer. Despite substantial changes in PET technology compared to PET/CT, initial studies have demonstrated that integrated PET/MR provides comparable image quality to that of PET/CT, retaining PET quantification efficacy. In this review we briefly describe technological changes compared to PET/CT that made integrated PET/MR possible, propose acquisition protocols for evaluation of prostate cancer with this new multimodal approach, present initial results concerning the application of PET/MR in prostate cancer, and outline the potential for further clinical applications, focusing on potential incremental value compared to present diagnostic performance.

Attenuation-corrected rest thallium-201/stress technetium 99m sestamibi myocardial SPECT in normals.

BackgroundRest thallium-201/stress technetium 99m sestamibi protocol is widely used in the clinical setting. Although attenuation correction (AC) represents an important recent development in cardiac single photon emission computed tomography (SPECT) imaging, adjacent extracardiac activity can affect the myocardial count density distribution on AC images, particularly with 201Tl. The aims of this study were to compare normal distribution between AC rest 201Tl and stress 99mTc-sestamibi SPECT images as well as to evaluate the effect of extracardiac activity on AC SPECT images with 99mTc and 201Tl.Methods and ResultsA phantom measurement and a study of 21 patients with low likelihood of coronary artery disease were performed with a triple-head SPECT system equipped with a americium 241 line source. In the phantom study, the presence of extracardiac activity increased the inferior-to-anterior ratios, particularly with 201Tl (1.01 to 1.32). In the clinical data, reduced count density with 201Tl compared to 99mTc-sestamibi was observed in most of the noninferior segments. On an individual segment basis, 37 (20%) of 189 segments from 11 (52%) of 21 subjects showed reduced count density on the 201Tl image compared to 99mTc-sestamibi by >10% of peak activity.ConclusionsThere is a significant difference in myocardial count density distribution between 99mTc-sestamibi and 201Tl on AC SPECT images, indicating that a careful image interpretation that considers the different normal count density distribution between the tracers and/or a tracer specific normal database is necessary, especially when defect reversibility is of concern. Further work should aim for the incorporation of scatter correction combined with attenuation correction.