Stefan P. Müller

Radioembolization with yttrium‐90 glass microspheres in hepatocellular carcinoma: European experience on safety and long‐term survival

Radioembolization has been demonstrated to allow locoregional therapy of patients with hepatocellular carcinoma not eligible for transarterial chemoembolization or other local therapies. The aim of this study was to validate evidence of the safety and efficacy of this treatment in a European sample of patients with advanced hepatocellular carcinoma (HCC). Therefore, 108 consecutive patients with advanced HCC and liver cirrhosis were included. Yttrium‐90 (Y‐90) microspheres were administered in a lobar fashion over the right or left branch of the hepatic artery. The response to treatment was evaluated by computed tomography (CT) imaging applying Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria with recent European Association for the Study of the Liver / National Cancer Institute (EASL/NCI) amendments. Time to progression (TTP) and overall survival were estimated by the Kaplan‐Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (±18) Gy. According to EASL criteria, complete responses were determined in 3% of patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue‐syndrome. Conclusion: Radioembolization with Y‐90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted. (HEPATOLOGY 2010;52:1741‐1749)

FDG-PET/CT in re-staging of patients with lymphoma

The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone (P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.

MR-based attenuation correction for torso-PET/MR imaging: pitfalls in mapping MR to CT data

PurposeMR-based attenuation correction (AC) will become an integral part of combined PET/MR systems. Here, we propose a toolbox to validate MR-AC of clinical PET/MRI data sets.MethodsTorso scans of ten patients were acquired on a combined PET/CT and on a 1.5-T MRI system. MR-based attenuation data were derived from the CT following MR–CT image co-registration and subsequent histogram matching. PET images were reconstructed after CT- (PETCT) and MR-based AC (PETMRI). Lesion-to-background (L/B) ratios were estimated on PETCT and PETMRI.ResultsMR–CT histogram matching leads to a mean voxel intensity difference in the CT- and MR-based attenuation images of 12% (max). Mean differences between PETMRI and PETCT were 19% (max). L/B ratios were similar except for the lung where local misregistration and intensity transformation leads to a biased PETMRI.ConclusionOur toolbox can be used to study pitfalls in MR-AC. We found that co-registration accuracy and pixel value transformation determine the accuracy of PETMRI.

The value of fluorine-18 fluorodeoxyglucose PET in patients with medullary thyroid cancer

Abstract.The early detection of metastases from medullary thyroid cancer (MTC) is important because the only curative therapy consists in surgical removal of all tumour tissue. There is no single sensitive diagnostic imaging modality for the localization of all metastases in patients with MTC. Therefore, in many cases several imaging modalities (e.g. ultrasonography, magnetic resonance imaging, computerized tomography and scintigraphy using pentavalent technetium-99m dimercaptosuccinic acid, thallium-201 chloride, indium-111 pentetreotide, anti-CEA antibodies or metaiodobenzylguanidine) must be performed consecutively in patients with elevated calcitonin levels until the tumour is localized. In this prospective study, we investigated the value of fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) in the follow-up of patients with MTC. [18F]FDG PET examinations of the neck and the chest were performed in 20 patients with elevated calcitonin levels or sonographic abnormalities in the neck. Positive [18F]FDG findings were validated by histology, computerized tomography or selective venous catheterization. [18F]FDG PET detected tumour in 13/17 patients (nine cases were validated by histology, four by computerized tomography). Five patients showed completely negative PET scans (of these cases, one was true-negative and four false-negative). One patient with [18F]FDG accumulation in pulmonary lesions from silicosis and one patient with a neck lesion that was not subjected to histological validation had to be excluded. Considering all validated localizations, [18F]FDG PET detected 12/14 tumour manifestations in the neck, 6/7 mediastinal metastases, 2/2 pulmonary metastases and 2/2 bone metastases. In two patients with elevated calcitonin levels, no diagnostic modality was able to localize a tumour. The sensitivity of [18F]FDG PET in the follow-up of MTC was 76% (95% confidence interval 53%–94%); this is encouraging. [18F]FDG PET promises to be a valuable diagnostic method, especially for the detection of lymph node metastases, surgical resection of which can result in complete remission.

Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer.

AimTo estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy. MethodsFifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1–21 GBq 131I using single activities of 1–6 GBq. The patients were stratified according to the cumulative activities into low-activity (1–2 GBq), middle-activity (3–7 GBq), and high-activity groups (9–21 GBq). The time–activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models. ResultsThe median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy·GBq−1 (range, 0.1–0.3 Gy·GBq−1) and 0.48 Gy·GBq−1 (range, 0.2–1.2 Gy·GBq−1), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups. ConclusionThe iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered 131I activity was not significantly decreased during the course of therapy. Comparing the well-known dose–effect relationships in external radiation therapy, the absorbed dose per administered 131I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of 131I in human salivary glands.

Person tracking in real-world scenarios using statistical methods

This paper presents a novel approach to robust and flexible person tracking using an algorithm that combines two powerful stochastic modeling techniques: pseudo-2D hidden Markov models (P2DHMM) used for capturing the shape of a person within an image frame, and the well-known Kalman-filtering algorithm, that uses the output of the P2DHMM for tracking the person by estimation of a bounding box trajectory indicating the location of the person within the entire video sequence. Both algorithms cooperate together in an optimal way, and with this co-operative feedback, the proposed approach even makes the tracking of people possible in the presence of background motions caused by moving objects or by camera operations as, e.g., panning or zooming. Our results are confirmed by several tracking examples in real scenarios, shown at the end of the paper and provided on the Web server of our institute.

Measures of performance in nonlinear estimation tasks: prediction of estimation performance at low signal-to-noise ratio.

Maximum-likelihood (ML) estimation is an established paradigm for the assessment of imaging system performance in nonlinear quantitation tasks. At high signal-to-noise ratio (SNR), ML estimates are asymptotically Gaussian-distributed, unbiased and efficient, thereby attaining the Cramer-Rao bound (CRB). Therefore, at high SNR the CRB is useful as a predictor of the variance of ML estimates and, consequently, as a basis for measures of estimation performance. At low SNR, however, the achievable parameter variances are often substantially larger than the CRB and the estimates are no longer Gaussian-distributed. These departures imply that inference about the estimates that is based on the CRB and the assumption of a normal distribution will not be valid. We have found previously that for some tasks these effects arise at noise levels considered clinically acceptable. We have derived the mathematical relationship between a new measure, chi2(pdf-ML), and the expected probability density of the ML estimates, and have justified the use of chi2(pdf-ML)-isocontours in parameter space to describe the ML estimates. We validated this approach by simulation experiments using spherical objects imaged with a Gaussian point spread function. The parameters, activity concentration and size, were estimated simultaneously by ML, and variances and covariances calculated over 1000 replications per condition from 3D image volumes and from 2D tomographic projections of the same object. At low SNR, where the CRB is no longer achievable, chi2(pdf-ML)-isocontours provide a robust prediction of the distribution of the ML estimates. At high SNR, the chi2(pdf-ML)-isocontours asymptotically approach the analogous chi2(pdf-F)-contours derived from the Fisher information matrix. The chi2(pdf-ML) model appears to be suitable for characterization of the influence of the noise level and characteristics, the task, and the object on the shape of the probability density of the ML estimates at low SNR. Furthermore, it provides unique insights into the causes of the variability of estimation performance.

Assessment of ventricular function with first-pass radionuclide angiography using technetium 99m hexakis-2-methoxyisobutylisonitrile: a European multicentre study.

In the context of a multicentre study on the use of technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi), we evaluated the accuracy of the ventricular function assessed at rest by means of first-pass radionuclide angiocardiography acquired during the injection of the tracer for myocardial perfusion scintigraphy. The results were compared with first-pass studies performed using reference tracers sodium pertechnetate Tc 99m or technetium 99m diethylene triamine penta-acetic acid or with gated radionuclide angiocardiography. A total of 66 patients of the 105 enrolled in the study could be evaluated. The comparison of the first-pass studies was possible in 33 subjects with regard to the left ventricular ejection fraction, yieldingr=0.909 (P< 10−6), and in 22 cases with regard to the right ventricular ejection fraction, yieldingr=0.712 (P<0.001). The comparison between the first-pass study using99mTc-Sestamibi and the equilibrium gated radionuclide angiocardiography was possible for the left ventricular ejection fraction in 26 cases, withr=0.937 (P<10−6), and for the right ventricular ejection fraction in 15 subjects, withr=0.783 (P<0.001). In conclusion, the assessment of ventricular function performed by acquiring a first-pass radionuclide angiocardiograph during the injection of99mTc-Sestamibi for perfusion myocardial scintigraphy can be considered reliable and accurate, when compared with the usually employed techniques. This result confirms the feasibility of a combined evaluation of perfusion and function at rest and during stress testing, which represents one of the most interesting advantages offered by the use of99mTc-Sestamibi.

A method for approximating the density of maximum-likelihood and maximum a posteriori estimates under a Gaussian noise model

The performance of maximum-likelihood (ML) and maximum a posteriori (MAP) estimates in non-linear problems at low data SNR is not well predicted by the Cramér-Rao or other lower bounds on variance. In order to better characterize the distribution of ML and MAP estimates under these conditions, we derive a point approximation to density values of the conditional distribution of such estimates. In an example problem, this approximate distribution captures the essential features of the distribution of ML estimates in the presence of Gaussian-distributed noise.

Improved Regional Activity Quantitation in Nuclear Medicine Using a New Approach to Correct for Tissue Partial Volume and Spillover Effects

We have developed a neσw method of compensating for effects of partial volume and spillover in dual-modality imaging. The approach requires segmentation of just a few tissue types within a small volume-of-interest (VOI) surrounding a lesion; the algorithm estimates simultaneously, from projection data, the activity concentration within each segmented tissue inside the VOI. Measured emission projections were fitted to the sum of resolution-blurred projections of each such tissue, scaled by its unknown activity concentration, plus a global background contribution obtained by reprojection through the reconstructed image volume outside the VOI. The method was evaluated using multiple-pinhole μSPECT data simulated for the MOBY mouse phantom containing two spherical lung tumors and one liver tumor, as well as using multiple-bead phantom data acquired on μSPECT and μCT scanners. Each VOI in the simulation study was 4.8 mm (12 voxels) cubed and, depending on location, contained up to four tissues (tumor, liver, heart, lung) with different values of relative 99mTc concentration. All tumor activity estimates achieved <; 3% bias after ~ 15 ordered-subsets expectation maximization (OSEM) iterations (×10 subsets), with better than 8% precision (≤ 25% greater than the Cramer-Rao lowσer bound). The projection-based fitting approach also outperformed three standardized uptake value (SUV)-like metrics, one of which was corrected for count spillover. In the bead phantom experiment, the mean ± standard deviation of the bias of VOI estimates of bead concentration were 0.9±9.5%, comparable to those of a perturbation geometric transfer matrix (pGTM) approach (-5.4±8.6%); however, VOI estimates were more stable with increasing iteration number than pGTM estimates, even in the presence of substantial axial misalignment between μCT and μSPECT image volumes.