Bernd Klaeser

PET-CT-guided interventions in the management of FDG-positive lesions in patients suffering from solid malignancies: initial experiences.

Positron emission tomography–computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.

Comparison of outcome and recurrence-free survival after sentinel lymph node biopsy and lymphadenectomy in vulvar cancer

OBJECTIVES Lymph node status is an important prognostic factor in patients with squamous cell carcinoma (SCC) of the vulva. Complete inguinofemoral lymph node dissection (ILND) is accompanied by a high morbidity. Sentinel lymph node biopsy (SLNB) was established for less invasive lymph node (LN) staging. The aim of this study was to evaluate safety of SLNB in terms of accuracy and outcome in a clinical routine setting. METHODS We retrospectively reviewed the data of patients who underwent SLNB and/or ILND for vulvar SCC in the years 1990-2007. Clinical follow-up was evaluated for histological nodal-negative patients with tumor stage T1 or T2. The false negative rate of SLNB was determined in patients who underwent both SLNB and ILND. RESULTS Preoperative sentinel lymph node (SLN) visualization by scintigraphy was successful in 95% of all patients. SLNB was false negative in 1/45 inguinae (2.2%). All SLN were detected intraoperatively. During the follow-up period (median 24 months for SLNB and 111 months for ILND), no groin recurrences in initially nodal negative patients occurred (n=34, 59 inguinae). Transient lymph edema occurred in 7/18 patients after ILND (39%) and 2/16 patients (13%) after SLNB. No persistent edemas were found after SLNB and ILND. CONCLUSION According to our experience SLNB is feasible and accurately predicts LN status of vulvar SCC under clinical routine conditions. SLNB in vulvar cancer seems to be a safe alternative to ILND in order to reduce morbidity of surgical treatment.

PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact.

PurposeIn a minority of cases a definite diagnosis and stage grouping in cancer patients is not possible based on the imaging information of PET/CT. We report our experience with percutaneous PET/CT-guided bone biopsies to histologically verify the aetiology of hypermetabolic bone lesions.MethodsWe retrospectively reviewed the data of 20 consecutive patients who underwent multimodal image-guided bone biopsies using a dedicated PET/CT system in a step-by-step technique. Technical and clinical success rates of PET/CT-guided biopsies were evaluated. Questionnaires were sent to the referring physicians to assess the impact of biopsies on patient management and to check the clinical need for PET/CT-guided biopsies.ResultsClinical indications for biopsy were to histologically verify the aetiology of metabolically active bone lesions without a morphological correlate confirming the suspicion of metastases in 15 patients, to determine the origin of suspected metastases in 3 patients and to evaluate the appropriateness of targeted therapy options in 2 patients. Biopsies were technically successful in all patients. In 19 of 20 patients a definite histological diagnosis was possible. No complications or adverse effects occurred. The result of PET/CT-guided bone biopsies determined a change of the planned treatment in overall 56% of patients, with intramodality changes, e.g. chemotherapy with palliative instead of curative intent, and intermodality changes, e.g. systemic therapy instead of surgery, in 22 and 50%, respectively.ConclusionPET/CT-guided bone biopsies are a promising alternative to conventional techniques to make metabolically active bone lesions—especially without a distinctive morphological correlate—accessible for histological verification. PET/CT-guided biopsies had a major clinical impact in patients who otherwise cannot be reliably stage grouped at the time of treatment decisions.

A navigation system for percutaneous needle interventions based on PET/CT images: Design, workflow and error analysis of soft tissue and bone punctures

Percutaneous needle intervention based on PET/CT images is effective, but exposes the patient to unnecessary radiation due to the increased number of CT scans required. Computer assisted intervention can reduce the number of scans, but requires handling, matching and visualization of two different datasets. While one dataset is used for target definition according to metabolism, the other is used for instrument guidance according to anatomical structures. No navigation systems capable of handling such data and performing PET/CT image-based procedures while following clinically approved protocols for oncologic percutaneous interventions are available. The need for such systems is emphasized in scenarios where the target can be located in different types of tissue such as bone and soft tissue. These two tissues require different clinical protocols for puncturing and may therefore give rise to different problems during the navigated intervention. Studies comparing the performance of navigated needle interventions targeting lesions located in these two types of tissue are not often found in the literature. Hence, this paper presents an optical navigation system for percutaneous needle interventions based on PET/CT images. The system provides viewers for guiding the physician to the target with real-time visualization of PET/CT datasets, and is able to handle targets located in both bone and soft tissue. The navigation system and the required clinical workflow were designed taking into consideration clinical protocols and requirements, and the system is thus operable by a single person, even during transition to the sterile phase. Both the system and the workflow were evaluated in an initial set of experiments simulating 41 lesions (23 located in bone tissue and 18 in soft tissue) in swine cadavers. We also measured and decomposed the overall system error into distinct error sources, which allowed for the identification of particularities involved in the process as well as highlighting the differences between bone and soft tissue punctures. An overall average error of 4.23 mm and 3.07 mm for bone and soft tissue punctures, respectively, demonstrated the feasibility of using this system for such interventions. The proposed system workflow was shown to be effective in separating the preparation from the sterile phase, as well as in keeping the system manageable by a single operator. Among the distinct sources of error, the user error based on the system accuracy (defined as the distance from the planned target to the actual needle tip) appeared to be the most significant. Bone punctures showed higher user error, whereas soft tissue punctures showed higher tissue deformation error.

Transconvolution and the virtual positron emission tomograph--a new method for cross calibration in quantitative PET∕CT imaging

PURPOSE Positron emission tomography (PET)∕computed tomography (CT) measurements on small lesions are impaired by the partial volume effect, which is intrinsically tied to the point spread function of the actual imaging system, including the reconstruction algorithms. The variability resulting from different point spread functions hinders the assessment of quantitative measurements in clinical routine and especially degrades comparability within multicenter trials. To improve quantitative comparability there is a need for methods to match different PET∕CT systems through elimination of this systemic variability. Consequently, a new method was developed and tested that transforms the image of an object as produced by one tomograph to another image of the same object as it would have been seen by a different tomograph. The proposed new method, termed Transconvolution, compensates for differing imaging properties of different tomographs and particularly aims at quantitative comparability of PET∕CT in the context of multicenter trials. METHODS To solve the problem of image normalization, the theory of Transconvolution was mathematically established together with new methods to handle point spread functions of different PET∕CT systems. Knowing the point spread functions of two different imaging systems allows determining a Transconvolution function to convert one image into the other. This function is calculated by convolving one point spread function with the inverse of the other point spread function which, when adhering to certain boundary conditions such as the use of linear acquisition and image reconstruction methods, is a numerically accessible operation. For reliable measurement of such point spread functions characterizing different PET∕CT systems, a dedicated solid-state phantom incorporating (68)Ge∕(68)Ga filled spheres was developed. To iteratively determine and represent such point spread functions, exponential density functions in combination with a Gaussian distribution were introduced. Furthermore, simulation of a virtual PET system provided a standard imaging system with clearly defined properties to which the real PET systems were to be matched. A Hann window served as the modulation transfer function for the virtual PET. The Hanns apodization properties suppressed high spatial frequencies above a certain critical frequency, thereby fulfilling the above-mentioned boundary conditions. The determined point spread functions were subsequently used by the novel Transconvolution algorithm to match different PET∕CT systems onto the virtual PET system. Finally, the theoretically elaborated Transconvolution method was validated transforming phantom images acquired on two different PET systems to nearly identical data sets, as they would be imaged by the virtual PET system. RESULTS The proposed Transconvolution method matched different PET∕CT-systems for an improved and reproducible determination of a normalized activity concentration. The highest difference in measured activity concentration between the two different PET systems of 18.2% was found in spheres of 2 ml volume. Transconvolution reduced this difference down to 1.6%. In addition to reestablishing comparability the new method with its parameterization of point spread functions allowed a full characterization of imaging properties of the examined tomographs. CONCLUSIONS By matching different tomographs to a virtual standardized imaging system, Transconvolution opens a new comprehensive method for cross calibration in quantitative PET imaging. The use of a virtual PET system restores comparability between data sets from different PET systems by exerting a common, reproducible, and defined partial volume effect.PURPOSE Positron emission tomography (PET)/computed tomography (CT) measurements on small lesions are impaired by the partial volume effect, which is intrinsically tied to the point spread function of the actual imaging system, including the reconstruction algorithms. The variability resulting from different point spread functions hinders the assessment of quantitative measurements in clinical routine and especially degrades comparability within multicenter trials. To improve quantitative comparability there is a need for methods to match different PET/CT systems through elimination of this systemic variability. Consequently, a new method was developed and tested that transforms the image of an object as produced by one tomograph to another image of the same object as it would have been seen by a different tomograph. The proposed new method, termed Transconvolution, compensates for differing imaging properties of different tomographs and particularly aims at quantitative comparability of PET/CT in the context of multicenter trials. METHODS To solve the problem of image normalization, the theory of Transconvolution was mathematically established together with new methods to handle point spread functions of different PET/CT systems. Knowing the point spread functions of two different imaging systems allows determining a Transconvolution function to convert one image into the other. This function is calculated by convolving one point spread function with the inverse of the other point spread function which, when adhering to certain boundary conditions such as the use of linear acquisition and image reconstruction methods, is a numerically accessible operation. For reliable measurement of such point spread functions characterizing different PET/CT systems, a dedicated solid-state phantom incorporating68 Ge/68 Ga filled spheres was developed. To iteratively determine and represent such point spread functions, exponential density functions in combination with a Gaussian distribution were introduced. Furthermore, simulation of a virtual PET system provided a standard imaging system with clearly defined properties to which the real PET systems were to be matched. A Hann window served as the modulation transfer function for the virtual PET. The Hanns apodization properties suppressed high spatial frequencies above a certain critical frequency, thereby fulfilling the above-mentioned boundary conditions. The determined point spread functions were subsequently used by the novel Transconvolution algorithm to match different PET/CT systems onto the virtual PET system. Finally, the theoretically elaborated Transconvolution method was validated transforming phantom images acquired on two different PET systems to nearly identical data sets, as they would be imaged by the virtual PET system. RESULTS The proposed Transconvolution method matched different PET/CT-systems for an improved and reproducible determination of a normalized activity concentration. The highest difference in measured activity concentration between the two different PET systems of 18.2% was found in spheres of 2 ml volume. Transconvolution reduced this difference down to 1.6%. In addition to reestablishing comparability the new method with its parameterization of point spread functions allowed a full characterization of imaging properties of the examined tomographs. CONCLUSIONS By matching different tomographs to a virtual standardized imaging system, Transconvolution opens a new comprehensive method for cross calibration in quantitative PET imaging. The use of a virtual PET system restores comparability between data sets from different PET systems by exerting a common, reproducible, and defined partial volume effect.

Metabolic Tumour Volume for Response Prediction in Advanced-Stage Hodgkin Lymphoma

18F-FDG PET/CT for staging Hodgkin lymphoma may allow for accurate and reliable assessment of the metabolic tumor volume (MTV) as a baseline risk factor. Our aim was to analyze the prognostic impact of MTV measurements obtained by different means in advanced-stage Hodgkin lymphoma patients treated within the German Hodgkin Study Group HD18 trial. Methods: Within HD18, 310 patients underwent 18F-FDG PET/CT scanning for staging, which was available to the central review panel for quantitative analysis. We calculated the MTV by 4 different thresholding methods and performed receiver-operating-characteristic analysis to evaluate the potential for prediction of early response determined by PET after 2 cycles (PET-2) of dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). Logistic regression was used to evaluate its prognostic value concerning progression-free survival and overall survival. Results: All of the different MTV calculations predicted PET-2 response to a moderate and comparable degree (area under the curve, 0.62–0.63; P = 0.01–0.06). With none of the measuring methods did the receiver-operating-characteristic curves point to any unique cutoffs; rather, a wide range of possible cutoffs was indicated. None of the MTV measurements was prognostic for progression-free survival (hazard ratio, 1.2–1.5; P = 0.15–0.52) or overall survival (hazard ratio, 1.0–1.5; P = 0.95–0.27). Conclusion: Baseline MTV as determined by different means is a predictive factor for early response to eBEACOPP after 2 cycles. However, value as a prognostic factor after a highly effective PET-2–adapted treatment strategy could not be observed.

Value of bone marrow biopsy in Hodgkin lymphoma patients staged by FDG PET: results from the German Hodgkin Study Group trials HD16, HD17, and HD18

Background Bone marrow (BM) involvement defines advanced-stage Hodgkin lymphoma and thus has impact on the assignment to treatment. Our aim was to evaluate whether the established BM biopsy may be omitted in patients if 18F-fluorodeoxyglucose positron emission tomography (PET) scanning is carried out during staging. Patients and methods Our analysis set consisted of 832 Hodgkin lymphoma patients from the German Hodgkin Study Group trials HD16, HD17, and HD18 who underwent both PET scanning and BM biopsy before treatment. All PET studies were centrally reviewed and BM was categorized as showing focal involvement or not. Results Taking BM biopsy as reference standard, baseline PET showed a negative predictive value of 99.9% [95% confidence interval (CI) 99.2% to 100%] with true-negative results in 702 of 703 cases. The sensitivity of PET for detecting BM involvement was 95.0% (95% CI 75.1% to 99.9%) as it could identify 19 out of 20 patients with positive BM biopsy. Moreover, PET found 110 additional subjects with focal BM lesions who would have been considered negative by biopsy. Conclusions When compared with BM biopsy, PET was able to detect focal BM lesions in a large number of additional patients. This indicates that conventional BM biopsy may substantially underestimate the actual incidence of BM involvement. Given the high negative predictive value, baseline PET scanning can safely be used to exclude BM involvement in Hodgkin lymphoma. BM biopsy should be considered only in such patients in whom PET-detected lesions lead to a change of treatment protocol. Registered trials The trials included in this analysis were registered at ClinicalTrials.gov: HD16-NCT00736320, HD17-NCT01356680, and HD18-NCT00515554.

Technical Note: Determination of individual thyroid clearance effective half-life with a common handheld electronic dosimeter

Purpose To determine the thyroid clearance effective half‐life Symbol with a common handheld electronic dosimeter (ED) in patients undergoing radioiodine treatment for hyperthyroidism. Symbol. No caption available. Methods Dose rates from 12 inpatients were measured daily with an ED and with a clinical uptake counter. The ED was attached to the patient with two different setups, one using a cervical collar and another employing a neck strap. Estimation of Symbol was performed by linear regression analysis of the log of both the ED and the uptake counter measurements versus time. The latter provided the reference data. Symbol. No caption available. Results Based on repeated neck strap dose rate measurements, individual Symbols were determined with clinically required accuracy. The mean difference from the reference method equaled to −0.09 ± 0.35 days. Symbol. No caption available. Conclusions Determination of individual Symbol is feasible with a common handheld ED using the simple and easy to instruct neck strap measurement setup. This simple method complements stationary uptake counter measurements and thus may improve the accuracy of radioiodine treatment planning by adding an individual Symbol for dose calculation. Symbol. No caption available. Symbol. No caption available.

Isotope independent determination of PET/CT modulation transfer functions from phantom measurements on spheres

PURPOSE A PET/CT systems imaging capabilities are best described by its point spread function (PSF) in the spatial domain or equivalently by its modulation transfer function (MTF) in the spatial frequency domain. Knowing PSFs or MTFs is a prerequisite for many numerical methods attempting to improve resolution and to reduce the partial volume effect. In PET/CT, the observed PSF is a convolution of the systems intrinsic imaging capabilities including image reconstruction (PSF0) and the positron range function (PRF) of the imaged β+ emitting isotope. A PRF describes the non-Gaussian distribution of β+ annihilation events around a hypothetical point source. The main aim was to introduce a new method for determining a PET/CT systems intrinsic MTF (MTF0) from phantom measurements of hot spheres independently of the β+ emitting isotope used for image acquisition. Secondary aim was to examine non-Gaussian and nonlinear MTFs of a modern iterative reconstruction algorithm. METHODS PET/CT images of seven phantom spheres with volumes ranging from 0.25 to 16 ml and filled either with 18F or with 68Ga were acquired and reconstructed using filtered back projection (FBP). MTFs were modeled with linear splines. The spline fit iteratively minimized the mean squared error between the acquired PET/CT image and a convolution of the thereof derived PSF with a numerical representation of the imaged hot phantom sphere. For determining MTF0, the numerical sphere representations were convolved with a PRF, simulating a fill with either 18F or 68Ga. The MTFs determined by this so-called MTF fit method were compared with MTFs derived from point source measurements and also compared with MTFs derived with a previously published PSF fit method. The MTF fit method was additionally applied to images reconstructed by a vendor iterative algorithm with PSF recovery (Siemens TrueX). RESULTS The MTF fit method was able to determine 18F and 68Ga dependent MTFs and MTF0 from FBP reconstructed images. Root-mean-square deviation between fit determined MTFs and point source determined MTFs ranged from 0.023 to 0.039. MTFs from Siemens TrueX reconstructions varied with size of the imaged sphere. CONCLUSIONS MTF0 can be determined regardless of the imaged isotope, when using existing PRF models for the MTF fit method presented. The method proves that modern iterative PET/CT reconstruction algorithms have nonlinear imaging properties. This behaviour is not accessible by point source measurements. MTFs resulting from these clinically applied algorithms need to be estimated from objects of similar geometry to those intended for clinical imaging.

Die Rolle der PET bei der bildgebenden Untersuchung von Patienten mit malignen Lymphomen

Positron-Emission-Tomography (PET) has emerged as a diagnostic gold standard for most tumor entities during the last 20 years, especially for patients suffering from malignant lymphoma. The development and distribution of machines allowing for hybrid imaging, i.e. the simultaneous acquisition of PET and CT datasets, and the possibility to assess even small pathologic findings with fused PET/CT image visualization, once more significantly improved the diagnostic accuracy of PET. Based on an excellent sensitivity the metabolic imaging with PET or PET/CT allows for a reliable overall assessment of patients with malignant lymphoma before therapy, for the early identification of non-responders during therapy, and for the diagnosis of relapse after therapy.