Stefan Delorme

Publications

• 2.09

  Impact points

  Automated vs. Manual Pattern Recognition of 3D (1)H MRSI Data of Patients with Prostate Cancer.

  Christian M Zechmann, Bjoern H Menze, B Michael Kelm, Patrik Zamecnik, Uwe Ikinger, Frederik L Giesel, Christian Thieke, Stefan Delorme, Fred A Hamprecht, Peter Bachert

  Academic radiology. 06/2012; 19(6):675-84.

  The aim of this study was to assess (1) automated analysis methods versus manual evaluation by human experts of three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) data from patients with prostate cancer and (2) the contribution of spatial information to decision making. Three-d... [more] The aim of this study was to assess (1) automated analysis methods versus manual evaluation by human experts of three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) data from patients with prostate cancer and (2) the contribution of spatial information to decision making. Three-dimensional proton MRSI was applied at 1.5 T. MRSI data from 10 patients with histologically proven prostate adenocarcinoma, scheduled either for prostatectomy or intensity-modulated radiation therapy, were evaluated. First, two readers manually labeled spectra using spatial information to identify the localization of spectra and neighborhood information, establishing the reference set of this study. Then, spectra were labeled again manually in a blinded and randomized manner and evaluated automatically using software that applied spectral line fitting as well as pattern recognition routines. Statistical analysis of the results of the different approaches was performed. Altogether, 1018 spectra were evaluable by all methods. Numbers of evaluable spectra differed significantly depending on patient and evaluation method. Compared to automated analysis, the readers made rather binary decisions, using information from neighboring spectra in ambiguous cases, when evaluating MRSI data as a whole. Differences between anatomically blinded and unblinded evaluation were larger than differences between evaluations using blinded data and automated techniques. An automated approach, which evaluates each spectrum individually, can be as good as an anatomy-blinded human reader. Spatial information is routinely used by human experts to support their final decisions. Automated procedures that consider anatomic information for spectral evaluation will enhance the diagnostic impact of MRSI of the human prostate.
• 2.74

  Impact points

  A phase II study for metabolic in vivo response monitoring with sequential 18FDG-PET-CT during treatment with the EGFR-monoclonal-antibody cetuximab in metastatic colorectal cancer: the Heidelberg REMOTUX trial.

  Anne K Berger, Carl von Gall, Ulrich Abel, Stefan Delorme, Matthias Kloor, Jennifer Ose, Tim F Weber, Annika Stange, Georg M Haag, Uwe Haberkorn, Florian Lordick, Dirk Jaeger

  BMC cancer. 03/2012; 12(1):108.

  ABSTRACT: BACKGROUND: The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely u... [more] ABSTRACT: BACKGROUND: The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely unclear. The understanding of mechanisms such as early changes in tumor metabolism is of clinical importance since there may be a substantial influence on choice and sequence of drug combinations. Early signals of response to cetuximab may prove useful to identify patients having a relevant clinical treatment benefit. The objective of this trial is to evaluate the predictive relevance of the relative change in 18 F-Fluorodeoxyglucose tumor uptake for early clinical response during short-term single agent treatment with cetuximab. Early clinical response will be routinely measured according to the response evaluation criteria in solid tumors. Accompanying research includes cytokine immune monitoring and analysis of tumor proteins and tumor genes. Methods/design The REMOTUX trial is an investigator-initiated, prospective, open-label, single-arm, single-center early exploratory predictive study. The first 18 F-FDG PET-CT is conducted at baseline followed by the run-in phase with cetuximab at days 1 and 8. At day 14, the second 18 F-FDG PET-CT is performed. Subsequently, patients are treated according to the Folfiri-cetuximab regimen as an active and approved first-line regimen for metastatic colorectal carcinoma. At day 56, clinical response is evaluated with a CT-scan compared to the baseline analysis. Tracer uptake is assessed using standardized uptake values (SUVs). The main hypothesis to be tested in the primary analysis is whether or not the relative change in the SUV from baseline to day 14 has any predictive relevance for early clinical response determined at day 56. Patients are followed until death from any cause or until 24 months after the last patient has ended trial treatment. DISCUSSION: The aim of this trial is to evaluate metabolic changes in metastatic colorectal cancer during short-term single agent treatment with cetuximab and to analyse their potential of predicting early clinical response. This could be helpful to answer the question if early identification of patients not responding to cetuximab is possible. Trial registration ClinicalTrials.gov NCT200811021020; EudraCT 200901327923.
• 2.09

  Impact points

  Parametric histogram analysis of dynamic contrast-enhanced MRI in multiple myeloma: a technique to evaluate angiogenic response to therapy?

  Christian M Zechmann, Lisa Traine, Tobias Meissner, Barbara Wagner-Gund, Frederik L Giesel, Hartmut Goldschmidt, Stefan Delorme, Jens Hillengass

  Academic radiology. 01/2012; 19(1):100-8.

  From dynamic contrast-enhanced magnetic resonance imaging, it is known that microcirculation patterns in multiple myeloma differ depending on the infiltration pattern. The purpose of this study was to evaluate histogram analysis of dynamic contrast-enhanced magnetic resonance imaging in MM to monito... [more] From dynamic contrast-enhanced magnetic resonance imaging, it is known that microcirculation patterns in multiple myeloma differ depending on the infiltration pattern. The purpose of this study was to evaluate histogram analysis of dynamic contrast-enhanced magnetic resonance imaging in MM to monitor early treatment response on the basis of microcirculation patterns. A total of 51 patients with multiple myeloma requiring therapy were examined. Dynamic contrast-enhanced magnetic resonance imaging of the lumbar spine was performed before and after conventional or high-dose chemotherapy with autologous stem cell transplantation. Statistical analysis included 245 vertebrae and dynamic microcirculation parameters as displayed in histograms. Resulting parameters (amplitude, exchange rate constant, skewness, kurtosis, and left shift) were correlated with therapeutic response. More than 70% of histograms derived from the microcirculation parameters showed a difference between the maximum peak before and after therapy (left shift). However, there was no significant difference between the particular treatment. Significantly different skewness of amplitude in 98% and kurtosis of exchange rate constant (94.1% and 98%) were seen in the patients who responded to treatment (P for each < .05). Histogram analysis revealed early changes after therapy resulting in a shift toward more (kurtosis) and lower values (skewness) of microcirculation parameters. Therefore, histogram analysis can determine and describe if a chosen therapy works at all. However, there were no differences between the chosen therapies. This needs to be reevaluated in a larger number of treated patients. Histogram analysis can also be an adjunct to a subjective visual analysis but is hampered by heterogeneous infiltration pattern seen in multiple myeloma.
• 2.02

  Impact points

  The feasibility of low mechanical index contrast enhanced ultrasound (CEUS) in distinguishing malignant from benign thoracic lesions.

  Nagmi R Qureshi, Christian Hintze, Frank Risse, Annette Kopp-Schneider, Ralf Eberhardt, Hans-Ulrich Kauczor, Stefan Delorme

  Ultrasound in medicine & biology. 09/2011; 37(11):1747-54.

  We proposed to assess the feasibility of low mechanical index (MI) contrast enhanced ultrasound (CEUS) in the characterisation of thoracic lesions. Fifty patients were prospectively examined by CEUS and images acquired on a low MI (0.17-0.24) setting following injection of SonoVue. From region-of-in... [more] We proposed to assess the feasibility of low mechanical index (MI) contrast enhanced ultrasound (CEUS) in the characterisation of thoracic lesions. Fifty patients were prospectively examined by CEUS and images acquired on a low MI (0.17-0.24) setting following injection of SonoVue. From region-of-interest (ROI) generated signal intensity (SI) time curves, the maximum SI, bolus arrival time (BAT), time to peak intensity (TTP), wash-in slope and mean transit time (MTT) were calculated. Using the Wilcoxon rank test; parameters and threshold values for positive differentiation were determined. In addition, for the parameters that allowed positive differentiation between malignant and benign lesions receiver operator curves (ROC) were obtained. The wash-in slope, TTP and MTT (p = 0.0003, <0.0001, 0.02) allowed positive differentiation. The sensitivity and specificity was 93% and 78%, with 6.87 s(-1) threshold value for the wash-in slope, 78% and 89% with 11.84 s threshold for the TTP and 48% and 89% with 78.6 s threshold for the MTT. CEUS is a useful tool for differentiating malignant and benign thoracic lesions.
• 4.60

  Impact points

  Diffusion-weighted imaging for non-invasive and quantitative monitoring of bone marrow infiltration in patients with monoclonal plasma cell disease: a comparative study with histology.

  Jens Hillengass, Tobias Bäuerle, Reiner Bartl, Mindaugas Andrulis, Fabienne McClanahan, Frederik B Laun, Christian Martin Zechmann, Rajiv Shah, Barbara Wagner-Gund, Dirk Simon, Christiane Heiss, Kai Neben, Anthony D Ho, Heinz-Peter Schlemmer, Hartmut Goldschmidt, Stefan Delorme, Bram Stieltjes

  British journal of haematology. 06/2011; 153(6):721-8.

  Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow biopsy or aspiration. Diffusion-weighted imaging (DWI) is a magnetic resonance imaging-technique that may mirror ... [more] Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow biopsy or aspiration. Diffusion-weighted imaging (DWI) is a magnetic resonance imaging-technique that may mirror tissue cellularity by measuring random movements of water molecules. To investigate if DWI is capable of assessing bone marrow cellularity in monoclonal plasma cell disease, we investigated 56 patients with multiple myeloma or monoclonal gammopathy of undetermined significance, and 30 healthy controls using DWI of the pelvis and/or the lumbar spine. In 25 of 30 patients who underwent biopsy, bone marrow trephine and DWI could be compared. Of the patients with symptomatic disease 15 could be evaluated after systemic treatment. There was a positive correlation between the DWI-parameter apparent diffusion coefficient (ADC) and bone marrow cellularity as well as micro-vessel density (P<0·001 respectively). ADC was significantly different between patients and controls (P<0·01) and before and after systemic therapy (P<0·001). In conclusion, DWI enabled bone marrow infiltration to be monitored in a non-invasive, quantitative way, suggesting that after further investigations on larger patient groups this might become an useful tool in the clinical work-up to assess tumour burden.
• 1.05

  Impact points

  On impulse response functions computed from dynamic contrast-enhanced image data by algebraic deconvolution and compartmental modeling.

  Gunnar Brix, Mona Salehi Ravesh, Stefan Zwick, Jürgen Griebel, Stefan Delorme

  Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB). 04/2011;

  Concentration-time courses measured by dynamic contrast-enhanced (DCE) imaging can be described by a convolution of the arterial input with an impulse response function, Q(T)(t), characterizing tissue microcirculation. Data analysis is based on two different approaches: computation of Q(T)(t) by alg... [more] Concentration-time courses measured by dynamic contrast-enhanced (DCE) imaging can be described by a convolution of the arterial input with an impulse response function, Q(T)(t), characterizing tissue microcirculation. Data analysis is based on two different approaches: computation of Q(T)(t) by algebraic deconvolution (AD) and subsequent evaluation according to the indicator dilution theory (IDT) or parameterization of Q(T)(t) by analytical expressions derived by compartmental modeling. Pitfalls of both strategies will be addressed in this study. Tissue data acquired by DCE-CT in patients with head-and-neck cancer and simulated by a reference model (MMID4) were analyzed by a two-compartment model (TCM), a permeability-limited two-compartment model (PL-TCM) and AD. Additionally, MMID4 was used to compute the 'true' response function that corresponds to the simulated tumor data. TCM and AD yielded accurate fits, whereas PL-TCM performed worse. Nevertheless, the corresponding response functions diverge markedly. The response curves obtained by TCM decrease exponentially in the early perfusion phase and overestimate the tissue perfusion, Q(T)(0). AD also resulted in response curves starting with a negative slope and not - as the 'true' response function in accordance with the IDT - with a horizontal plateau. They are thus not valid responses in the sense of the IDT that can be used unconditionally for parameter estimation. Response functions differing considerably in shape can result in virtually identical tissue curves. This non-uniqueness makes a strong argument not to use algebraic but rather analytical deconvolution to reduce the class of solutions to representatives that are in accordance with a-priori knowledge. To avoid misinterpretations and systematic errors, users must be aware of the pitfalls inherent to the different concepts.
• 4.85

  Impact points

  Dynamic contrast-enhanced ultrasound for assessment of skeletal muscle microcirculation in peripheral arterial disease.

  Erick Amarteifio, Marc-André Weber, Stephanie Wormsbecher, Serdar Demirel, Holger Krakowski-Roosen, Andreas Jöres, Simone Braun, Stefan Delorme, Dittmar Böckler, Hans-Ulrich Kauczor, Martin Krix

  Investigative radiology. 04/2011; 46(8):504-8.

  : This feasibility study was performed to assess whether dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion are able to detect alterations in the microvascular perfusion and arterial perfusion reserve in patients suffering from peripheral arterial disease (PAD) in compariso... [more] : This feasibility study was performed to assess whether dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion are able to detect alterations in the microvascular perfusion and arterial perfusion reserve in patients suffering from peripheral arterial disease (PAD) in comparison with healthy volunteers. : Twenty patients with PAD, Rutherford classification grade I, category III (mean age, 64 years; mean height, 173 cm; mean weight, 81.8 kg), and 20 volunteers (mean age, 50 years; mean height, 174 cm; mean weight, 77.8 kg) participated in the study. Low-mechanical index CEUS (7 MHz; MI, 0.28) was performed to the dominant lower leg after start of a continuous automatic intravenous injection of 4.8 mL suspension with microbubbles containing sulfur hexafluoride (SonoVue) within 5 minutes. Perfusion of the calf muscle was monitored by CEUS before, during, and after release of arterial occlusion at the thigh level lasting for 60 seconds. Several parameters, especially the time to maximum enhancement after release of occlusion (tmax), the maximum enhancement after release of occlusion (maxenh), the total vascular response after release of occlusion (AUCpost), and the resulting slope (m2) to maximum enhancement were calculated. : After release of the occlusion, a significantly delayed increase of the CEUS signal to maxenh was observed in the patients with PAD (32 ± 17 seconds) compared with volunteers (17 ± 8 seconds, P = 0.0009). maxenh was 66.5 ± 36.6 (∼mL) in PAD versus 135.6 ± 75.1 (∼mL) in volunteers (P = 0.0016). AUCpost was 3016.5 ± 1825.8 (∼mL·s) in PAD versus 5906.4 ± 3173.1 (∼mL·s) in volunteers (P = 0.0013), and m2 was significantly lower in PAD (3.8 ± 5.2 vs. 14.8 ± 9.7 [∼mL/s], P = 0.0001). : Microvascular perfusion deficits and reduced arterial perfusion reserve in patients with PAD are clearly detectable with dynamic CEUS after transient arterial occlusion.
• 1.27

  Impact points

  Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging of bone marrow in healthy individuals.

  Jens Hillengass, Bram Stieltjes, Tobias Bäuerle, Fabienne McClanahan, Christiane Heiss, Thomas Hielscher, Barbara Wagner-Gund, Verena Habetler, Hartmut Goldschmidt, Heinz-Peter Schlemmer, Stefan Delorme, Christian M Zechmann

  Acta radiologica (Stockholm, Sweden : 1987). 04/2011; 52(3):324-30.

  Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) displays microcirculation and permeability by application of contrast-media and diffusion-weighted imaging (DWI) is a tool for quantification of cellularity in the investigated area. Recently published examples cover breast cancer, CNS t... [more] Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) displays microcirculation and permeability by application of contrast-media and diffusion-weighted imaging (DWI) is a tool for quantification of cellularity in the investigated area. Recently published examples cover breast cancer, CNS tumors, head and neck cancer, gastrointestinal cancer, prostate cancer as well as hematologic malignancies. To investigated the influence of age, sex, and localization of the investigated region on findings of DCE-MRI and DWI. DCE-MRI-parameters amplitude A and exchange rate constant kep as well as the DWI-parameter ADC of the bone marrow of the lumbar vertebral column of 30 healthy individuals covering the typical range of age of tumor patients were evaluated. ADC was calculated using b=0 and a maximal b value of either 400 or 750 s/mm(2). Amplitude A of DCE-MRI decreased with age (P = 0.01) and amplitude A, exchange rate constant kep as well as ADC based on b = 400 s/mm(2) and b = 750 s/mm(2,) respectively, decreased significantly from the first to the fifth lumbar vertebra with P = 0.02, P = 0.05, P = 0.003, and P = 0.002, respectively. Quantitative parameters of functional imaging techniques in bone marrow are influenced by the age of the examined individual and the anatomical location of the investigated region.
• 3.23

  Impact points

  Enhancing pancreatic adenocarcinoma delineation in diffusion derived intravoxel incoherent motion f-maps through automatic vessel and duct segmentation.

  Thomas J Re, Andreas Lemke, Miriam Klauss, Fredrik B Laun, Dirk Simon, Katharina Grünberg, Stefan Delorme, Lars Grenacher, Riccardo Manfredi, Roberto Pozzi Mucelli, Bram Stieltjes

  Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 03/2011; 66(5):1327-32.

  Diffusion-based intravoxel incoherent motion imaging has recently gained interest as a method to detect and characterize pancreatic lesions, especially as it could provide a radiation- and contrast agent-free alternative to existing diagnostic methods. However, tumor delineation on intravoxel incohe... [more] Diffusion-based intravoxel incoherent motion imaging has recently gained interest as a method to detect and characterize pancreatic lesions, especially as it could provide a radiation- and contrast agent-free alternative to existing diagnostic methods. However, tumor delineation on intravoxel incoherent motion-derived parameter maps is impeded by poor lesion-to-pancreatic duct contrast in the f-maps and poor lesion-to-vessel contrast in the D-maps. The distribution of the diffusion and perfusion parameters within vessels, ducts, and tumors were extracted from a group of 42 patients with pancreatic adenocarcinoma. Clearly separable combinations of f and D were observed, and receiver operating characteristic analysis was used to determine the optimal cutoff values for an automated segmentation of vessels and ducts to improve lesion detection and delineation on the individual intravoxel incoherent motion-derived maps. Receiver operating characteristic analysis identified f = 0.28 as the cutoff for vessels (Area under the curve (AUC) = 0.901) versus tumor/duct and D = 1.85 μm(2) /ms for separating duct from tumor tissue (AUC = 0.988). These values were incorporated in an automatic segmentation algorithm and then applied to 42 patients. This yielded clearly improved tumor delineation compared to individual intravoxel incoherent motion-derived maps. Furthermore, previous findings that indicated that the f value in pancreatic cancer is strongly reduced compared to healthy pancreatic tissue were reconfirmed.
• 4.85

  Impact points

  Intravoxel incoherent motion MRI for the differentiation between mass forming chronic pancreatitis and pancreatic carcinoma.

  Miriam Klauss, Andreas Lemke, Katharina Grünberg, Dirk Simon, Thomas J Re, Mortiz N Wente, Frederik B Laun, Hans-Ulrich Kauczor, Stefan Delorme, Lars Grenacher, Bram Stieltjes

  Investigative radiology. 01/2011; 46(1):57-63.

  To determine which of the quantitative parameters obtained from intravoxel incoherent motion diffusion weighted imaging (DWI) is the most significant for the differentiation between pancreatic carcinoma and mass-forming chronic pancreatitis. Twenty-nine patients with pancreatic masses were included,... [more] To determine which of the quantitative parameters obtained from intravoxel incoherent motion diffusion weighted imaging (DWI) is the most significant for the differentiation between pancreatic carcinoma and mass-forming chronic pancreatitis. Twenty-nine patients with pancreatic masses were included, 9 proved to have a mass-forming pancreatitis and 20 had a pancreatic carcinoma. The patients were studied using intravoxel incoherent motion DWI with 11 b-values and the apparent diffusion coefficient (ADC), the true diffusion constant (D) and the perfusion fraction (f) were calculated. The diagnostic strength of the parameters was evaluated using receiver operating characteristic analysis. The ADC in chronic pancreatitis was higher than in pancreatic carcinoma with significant differences at b = 50, 75, 100, 150, 200, 300 s/mm (ADC50 = 3.17 ± 0.67 vs. 2.55 ± 1.09, ADC75 = 2.46 ± 0.4 vs. 1.93 ± 0.52, ADC100 = 2.28 ± 0.48 vs. 1.73 ± 0.45, ADC150 = 1.97 ± 0.26 vs. 1.63 ± 0.40, ADC200 = 1.98 ± 0.24 vs. 1.53 ± 0.28, and ADC300 = 1.76 ± 0.19 vs. 1.46 ± 0.31 × 10(-3) mm2/s). No significant differences were found at b = 25, 400, 600, and 800 s/mm (ADC25 = 4.69 ± 0.65 vs. 4.04 ± 1.35, ADC400 = 1.57 ± 0.21 vs. 1.37 ± 0.30, ADC600 = 1.38 ± 0.18 vs. 1.24 ± 0.25, and ADC800 = 1.27 ± 0.10 vs. 1.18 ± 0.19 × 10(-3) mm2/s) nor using ADCtot (1.42 ± 0.23 vs. 1.28 ± 0.12 × 10(-3) mm2/s). The perfusion fraction f was significantly higher in pancreatitis compared with pancreatic carcinoma (16.3% ± 5.30% vs. 8.2% ± 4.00%, P = 0.0001). There was no significant difference between groups for D (1.07 ± 0.224 × 10(-3) mm2/s for chronic pancreatitis and 1.09 ± 0.3 × 10(-3) mm2/s for pancreatic carcinoma, P = 0.66). For f, the highest area under the curve (0.894) and combined sensitivity (80%) and specificity (89.9%) were found. There were significant differences in ADC50-300 between chronic pancreatitis and pancreatic carcinoma. Because D is not significantly different between groups, differences in ADC can be attributed mainly to differences in perfusion. The perfusion fraction f proved to be the superior DWI-derived parameter for differentiation of mass-forming pancreatitis and pancreatic carcinoma.

• Imaging in multiple myeloma.

  Stefan Delorme, Andrea Baur-Melnyk

  Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer. 01/2011; 183:133-47.

  In multiple myeloma, imaging is required to determine the stage of disease and to anticipate impending bone fractures. Whereas the traditionally used Durie and Salmon staging system includes lytic bone lesions in plain films as criteria, modern systems include MRI findings. MRI is most sensitive to ... [more] In multiple myeloma, imaging is required to determine the stage of disease and to anticipate impending bone fractures. Whereas the traditionally used Durie and Salmon staging system includes lytic bone lesions in plain films as criteria, modern systems include MRI findings. MRI is most sensitive to both diffuse bone marrow involvement as well as solid plasma cell tumors. Whole-body low-dose CT (WBCT) may replace plain films in the near future, since it is quicker, more sensitive, and is better tolerated by patients. Intramedullary lesions are well seen as long as they are located in long bones where they are surrounded by fat. Diffuse bone marrow infiltration as well as intravertebral lesions, however, are difficult to detect with WBCT in the absence of frank destruction of cancellous bone. PET or PET-CT with 18-fluoro-deoxyglucose (FDG) are insensitive to diffuse bone marrow infiltration, but may help to assess treatment response in solitary or multiple solid plasma cell tumors which have a high FDG uptake before treatment.
• 6.34

  Impact points

  Staging monoclonal plasma cell disease: comparison of the Durie-Salmon and the Durie-Salmon PLUS staging systems.

  Kerstin Fechtner, Jens Hillengass, Stefan Delorme, Christiane Heiss, Kai Neben, Hartmut Goldschmidt, Hans-Ulrich Kauczor, Marc-André Weber

  Radiology. 10/2010; 257(1):195-204.

  To investigate the concordance of the Durie-Salmon staging system with the Durie-Salmon PLUS staging system in monoclonal plasma cell disease. Institutional review board approval was obtained, with waiver of informed consent. Lesions in 403 untreated patients (age range, 21-83 years) with monoclonal... [more] To investigate the concordance of the Durie-Salmon staging system with the Durie-Salmon PLUS staging system in monoclonal plasma cell disease. Institutional review board approval was obtained, with waiver of informed consent. Lesions in 403 untreated patients (age range, 21-83 years) with monoclonal gammopathy of undetermined significance (MGUS) (n = 84), solitary plasmacytoma (n = 17), amyloid light-chain amyloidosis (n = 12), and multiple myeloma (MM) (n = 290) were first staged on the basis of the classic Durie-Salmon staging system, which included conventional radiography. After examination with whole-body (WB) magnetic resonance (MR) imaging, lesions in these patients were, in addition, staged by using the Durie-Salmon PLUS staging system. Bone marrow infiltration pattern and focal lesions described as intramedullary, transcortical, and soft-tissue lesions, were assessed. The staging levels of both systems were compared. Of 84 patients with MGUS, lesions in 33 (39%) would have been staged differently with Durie-Salmon PLUS staging system when compared with Durie-Salmon staging system (stage I MM [37%], stage II MM [0%], and stage III MM [2%]). All 17 patients with plasmacytoma showed additional focal lesions or a diffuse infiltration leading to a classification as stage I MM (76%), stage II MM (12%), or stage III MM (12%) with Durie-Salmon PLUS. Of the 149 patients with stage I MM, lesions in 81 (54%) would have been staged differently with the Durie-Salmon PLUS staging system. Of the 21 patients with stage II MM, lesions in 19 (91%) would have been staged differently with Durie-Salmon PLUS staging system when compared with the Durie-Salmon staging system. Of the 120 patients with stage III MM, lesions in 72 (60%) would have been staged differently with the Durie-Salmon PLUS staging system. Given the fact that the Durie-Salmon and Durie-Salmon PLUS staging systems were concordant in only 45% of all examined patients with monoclonal plasma cell disease, in most cases, treatment decisions depend on the staging system used and, thus, remain a matter of debate.
• 17.79

  Impact points

  Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma.

  Jens Hillengass, Kerstin Fechtner, Marc-André Weber, Tobias Bäuerle, Sofia Ayyaz, Christiane Heiss, Thomas Hielscher, Thomas M Moehler, Gerlinde Egerer, Kai Neben, Anthony D Ho, Hans-Ulrich Kauczor, Stefan Delorme, Hartmut Goldschmidt

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 02/2010; 28(9):1606-10.

  With whole-body magnetic resonance imaging (wb-MRI), almost the whole bone marrow compartment can be examined in patients with monoclonal plasma cell disease. Focal lesions (FLs) detected by spinal MRI have been of prognostic significance in symptomatic multiple myeloma (sMM). In this study, we inve... [more] With whole-body magnetic resonance imaging (wb-MRI), almost the whole bone marrow compartment can be examined in patients with monoclonal plasma cell disease. Focal lesions (FLs) detected by spinal MRI have been of prognostic significance in symptomatic multiple myeloma (sMM). In this study, we investigated the prognostic significance of FLs in wb-MRI in patients with asymptomatic multiple myeloma (aMM). Wb-MRI was performed in 149 patients with aMM. The prognostic significance of the presence and absence, as well as the number, of FLs for progression into sMM was analyzed. FLs were present in 28% of patients. The presence per se of FLs and a number of greater than one FL were the strongest adverse prognostic factors for progression into sMM (P < .001) in multivariate analysis. A diffuse infiltration pattern in MRI, a monoclonal protein of 40 g/L or greater, and a plasma cell infiltration in bone marrow of 20% or greater were other adverse prognostic factors for progression-free survival in univariate analysis. We recommend use of wb-MRI for risk stratification of patients with asymptomatic multiple myeloma.
• 2.65

  Impact points

  Comparison of transient arterial occlusion and muscle exercise provocation for assessment of perfusion reserve in skeletal muscle with real-time contrast-enhanced ultrasound.

  Martin Krix, Holger Krakowski-Roosen, Erick Armarteifio, Susanne Fürstenberger, Stefan Delorme, Hans-Ulrich Kauczor, Marc-André Weber

  European journal of radiology. 12/2009;

  OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is able to quantify muscle perfusion and changes in perfusion due to muscle exercise in real-time. However, reliable measurement of standardized muscle exercise is difficult to perform in clinical examinations. We compared perfusion reserve assessed by ... [more] OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is able to quantify muscle perfusion and changes in perfusion due to muscle exercise in real-time. However, reliable measurement of standardized muscle exercise is difficult to perform in clinical examinations. We compared perfusion reserve assessed by CEUS after transient arterial occlusion and exercise to find the most suitable measurement for clinical application. METHODS: Contrast pulse sequencing (7MHz) during continuous IV infusion of SonoVue((R)) (4.8mL/300s) was used in 8 healthy volunteers to monitor muscle perfusion of the gastrocnemius muscle during transient (1min) arterial occlusion produced by a thigh cuff of a venous occlusion plethysmograph. Isometric muscle exercise (50% of individual maximum strength for 20s) was subsequently performed during the same examination, and several CEUS parameters obtained from ultrasound-signal-intensity-time curves and its calculation errors were compared. RESULTS: The mean maximum local blood volume after occlusion was 13.9 [ approximately mL] (range, 4.5-28.8 [ approximately mL]), and similar values were measured after sub-maximum exercise 13.8 [ approximately mL], (range, 4.6-22.2 [ approximately mL]. The areas under the curve during reperfusion vs. recovery were also similar (515.2+/-257.5 compared to 482.2+/-187.5 [ approximately mLs]) with a strong correlation (r=0.65), as were the times to maximum (15.3s vs. 15.9s), with a significantly smaller variation for the occlusion method (+/-2.1s vs. +/-9.0s, p=0.03). The mean errors for all calculated CEUS parameters were lower for the occlusion method than for the exercise test. CONCLUSIONS: CEUS muscle perfusion measurements can be easily performed after transient arterial occlusion. It delivers data which are comparable to CEUS measurements after muscle exercise but with a higher robustness. This method can be easily applied in clinical examination of patients with e.g. PAOD or diabetic microvessel diseases to assess perfusion reserve.
• 4.85

  Impact points

  Differentiation of Pancreas Carcinoma From Healthy Pancreatic Tissue Using Multiple b-Values: Comparison of Apparent Diffusion Coefficient and Intravoxel Incoherent Motion Derived Parameters.

  Andreas Lemke, Frederik Laun, Miriam Klau, Thomas Re, Dirk Simon, Stefan Delorme, Lothar Schad, Bram Stieltjes

  Investigative radiology. 10/2009;

  OBJECTIVES:: To evaluate in detail the diagnostic performance of diffusion-weighted imaging (DWI) to differentiate pancreas carcinoma from healthy pancreas using the apparent diffusion coefficient (ADC) and parameters derived from the intravoxel incoherent motion (IVIM) theory. MATERIALS AND METHODS... [more] OBJECTIVES:: To evaluate in detail the diagnostic performance of diffusion-weighted imaging (DWI) to differentiate pancreas carcinoma from healthy pancreas using the apparent diffusion coefficient (ADC) and parameters derived from the intravoxel incoherent motion (IVIM) theory. MATERIALS AND METHODS:: Twenty-three patients with pancreas carcinoma and 14 volunteers with healthy pancreas were examined at 1.5 Tesla using a single-shot echo-planar imaging DWI pulse sequence. Eleven b-values ranging from 0 to 800 s/mm were used. The acquisition was separated into blocks (b0, b25), (b0, b50),...(b0, b800) and each block was acquired in a single expirational breath-hold (TA = 26 seconds) to avoid motion artifacts. The ADC was calculated for all b-values using linear regression yielding ADCtot. By applying the IVIM model, which allows for the estimation of perfusion effects in DWI, the perfusion fraction f and the perfusion free diffusion parameter D were calculated. The diagnostic performance of ADC, f and D as a measure for the differentiation between healthy pancreas and pancreatic carcinoma was evaluated with receiver operating characteristics analysis. RESULTS:: In the healthy control group, the ADCtot ranged from 1.53 to 2.01 mum/ms with a mean value of 1.71 +/- 0.19 mum/ms, the perfusion fraction f ranged from 18.5% to 40.4% with a mean value of 25.0 +/- 6.2%, and the diffusion coefficient D from 0.94 to 1.28 mum/ms with a mean value of 1.13 +/- 0.15 mum/ms. In patients with pancreas carcinoma, the ADCtot ranged from 0.98 to 1.81 mum/ms with a mean value of 1.31 +/- 0.24 mum/ms, the perfusion fraction f ranged from 0% to 20.4% with a mean value of 8.59 +/- 4.6% and the diffusion coefficient D from 0.74 to 1.60 mum/ms with a mean value of 1.15 +/- 0.22 mum/ms. In comparison to healthy pancreatic tissue, a significant reduction of the perfusion fraction f and of ADCtot was found in pancreatic carcinoma (P < 0.00001, 0.0002, respectively). The f value showed more than a 10-fold higher significance level in distinguishing cancerous from normal tissue when compared with the ADCtot value. No significant difference in the diffusion coefficient D was observed between the 2 groups (P > 0.5). In the receiver operating characteristic-analyses, the area under curve for f was 0.991 and significantly larger than ADCtot (P < 0.05). f had the highest sensitivity, specificity, negative predictive value, and positive predictive value with 95.7%, 100%, 93.3%, and 100%, respectively. CONCLUSIONS:: Using the IVIM-approach, the f value proved to be the best parameter for the differentiation between healthy pancreas and pancreatic cancer. The acquisition of several b-values strongly improved the stability of the parameter estimation thus increasing the sensitivity and specificity to 95.7% and 100% respectively. The proposed method may hold great promise for the non invasive, noncontrast-enhanced imaging of pancreas lesions and may eventually become a screening tool for pancreatic cancer.
• 6.34

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  Multiple myeloma and monoclonal gammopathy of undetermined significance: importance of whole-body versus spinal MR imaging.

  Tobias Bäuerle, Jens Hillengass, Kerstin Fechtner, Christian M Zechmann, Lars Grenacher, Thomas M Moehler, Heiss Christiane, Barbara Wagner-Gund, Kai Neben, Hans-Ulrich Kauczor, Hartmut Goldschmidt, Stefan Delorme

  Radiology. 09/2009; 252(2):477-85.

  PURPOSE: To examine if standard magnetic resonance (MR) imaging of the axial skeleton is sufficient for evaluation of patients with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) or if whole-body MR is necessary. MATERIALS AND METHODS: A total of 100 untreated pat... [more] PURPOSE: To examine if standard magnetic resonance (MR) imaging of the axial skeleton is sufficient for evaluation of patients with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) or if whole-body MR is necessary. MATERIALS AND METHODS: A total of 100 untreated patients with MGUS (n = 27) or any stages of MM (n = 73) were examined with whole-body MR imaging and MR imaging of the axial skeleton. The study was approved by the institutional ethics committee, and written informed consent was given. Spinal pattern ("no diffuse involvement" or "diffuse involvement" as assessed from the signal intensity of the spinal bone marrow), serum parameters, and stage of disease were correlated with the probability of detecting extra-axial lesions with and without destruction of cortical bone by using a multiple logistic regression model. RESULTS: Of 100 patients, 39 had lesions in the axial skeleton and 37 had lesions in the extra-axial skeleton. Of the latter group, nine patients had no axial lesions and 13 patients had lesions that violated cortical bone, which implied an increased fracture risk. Because of the extraaxial location, lesions in these patients could be diagnosed with whole-body MR only. In addition, no single or combination of clinical factors observed (stage of disease, serum parameters, and spinal pattern) allowed investigators to identify patients with a significantly increased probability of having extra-axial lesions or lesions violating cortical bone. CONCLUSION: Whole-body MR imaging has potential for use in the initial work-up of patients with MGUS or MM, since almost one-half of all observed lesions would have been missed by using spinal MR imaging only and clinical parameters could not exclude the presence of extra-axial lesions.
• 2.02

  Impact points

  Real-Time Contrast-Enhanced Ultrasound for the Assessment of Perfusion Dynamics in Skeletal Muscle.

  Martin Krix, Holger Krakowski-Roosen, Hans-Ulrich Kauczor, Stefan Delorme, Marc-André Weber

  Ultrasound in medicine & biology. 09/2009;

  We developed a real-time low-MI contrast-enhanced ultrasound method (CEUS), compared it with venous occlusion plethysmography (VOP) and evaluated its robustness in the quantification of skeletal muscle perfusion during exercise. Contrast pulse sequencing (7MHz) during continuous intravenous infusion... [more] We developed a real-time low-MI contrast-enhanced ultrasound method (CEUS), compared it with venous occlusion plethysmography (VOP) and evaluated its robustness in the quantification of skeletal muscle perfusion during exercise. Contrast pulse sequencing (7MHz) during continuous intravenous infusion of SonoVue (4.8mL/300s) was used repeatedly in eight healthy volunteers to monitor changes of the muscle perfusion before, during and after isometric exercises (10 to 50% of individual maximum strength for 20 to 30 s) of the gastrocnemius muscle in real time. CEUS was correlated with VOP at different time points, and the exactness of several CEUS parameters obtained from ultrasound-signal-intensity-time curves was evaluated. Real-time CEUS depicted a large variability of the skeletal muscle blood volume at rest (mean, 3.48; range, 0.60 to 9.92 [ approximately mL]), with a significant reproducibility (r=0.72, p<0.05) and correlation with VOP (r=0.59, p<0.001). Mean blood volume during exercise was 1.58( approximately mL), increased to a mean maximum after exercise of 8.88( approximately mL), the mean change of the local blood volume during and directly after the exercise was -0.10 and +1.57( approximately mL/s). The average CEUS signal during exercise decreased (mean area under the curve, -50.4[ approximately mL.s]) and subsequently increased post exercise (mean 118.6[ approximately mL.s]). CEUS parameters could be calculated with mean relative errors between 6 and 36%. Continuous assessment of local muscle microcirculation during exercise is possible with real-time CEUS with an acceptable robustness. Its application may be of particular interest in a better understanding of the role of perfusion during muscle training, and the monitoring of pathological vascular response, such as in diabetic microvessel diseases.
• 2.65

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  Changes in the micro-circulation of skeletal muscle due to varied isometric exercise assessed by contrast-enhanced ultrasound.

  Martin Krix, Marc-André Weber, Hans-Ulrich Kauczor, Stefan Delorme, Holger Krakowski-Roosen

  European journal of radiology. 06/2009;

  PURPOSE: To quantitatively assess local muscle micro-circulation with real-time contrast-enhanced ultrasound (CEUS) during different exercises and compare the results with performed muscle work and global blood flow. MATERIALS AND METHODS: Sixteen low mechanical index CEUS examinations of the right ... [more] PURPOSE: To quantitatively assess local muscle micro-circulation with real-time contrast-enhanced ultrasound (CEUS) during different exercises and compare the results with performed muscle work and global blood flow. MATERIALS AND METHODS: Sixteen low mechanical index CEUS examinations of the right lower leg flexors of healthy volunteers were performed using a continuous infusion of SonoVue((R)) (4.8mL/300s). Several muscle perfusion parameters were extracted from derived CEUS signal intensity time curves during different isometric exercises (10-50% of maximum individual strength for 20-30s) and then correlated with the performed muscle work or force, and the whole lower leg blood flow which we measured simultaneously by venous occlusion plethysmography (VOP). RESULTS: The shapes of the CEUS curve during and after exercise differed individually depending on the performed muscle work. The maximum blood volume MAX was observed only after exercise cessation and was significantly correlated with the performed muscle force (r=0.77, p<0.0001). The blood volume over exercise time was inversely correlated with the spent muscle work (r=-0.60, p=0.006). CEUS and VOP measurements correlated only at rest and after the exercise. During exercise, mean CEUS local blood volume decreased (from 3.48 to 2.19 ( approximately mL)), while mean VOP global blood flow increased (mean, from 3.96 to 7.71mL/100mg/min). CONCLUSION: Real-time low-MI CEUS provides complementary information about the local muscle micro-circulation compared to established blood flow measures. CEUS may be used for a better understanding of muscle perfusion physiology and in the diagnosis of micro-circulation alterations such as in peripheral arterial occlusive disease or diabetic angiopathy.
• 6.75

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  Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation.

  Jens Hillengass, Christian Zechmann, Tobias Bäuerle, Barbara Wagner-Gund, Christiane Heiss, Axel Benner, Anthony Ho, Kai Neben, Dirk Hose, Hans-Ulrich Kauczor, Hartmut Goldschmidt, Stefan Delorme, Thomas Moehler

  Clinical cancer research : an official journal of the American Association for Cancer Research. 04/2009;

  PURPOSE: The aim of our study was to investigate whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows visualization of changes in microcirculation between healthy controls on the one side and early/advanced stages of plasma cell disease on the other.EXPERIMENTAL DESIGN: We e... [more] PURPOSE: The aim of our study was to investigate whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows visualization of changes in microcirculation between healthy controls on the one side and early/advanced stages of plasma cell disease on the other.EXPERIMENTAL DESIGN: We examined a group of 222 individuals consisting of 60 patients with monoclonal gammopathy of undetermined significance (MGUS), 65 patients with asymptomatic multiple myeloma (aMM), 75 patients with newly diagnosed symptomatic MM (sMM), and 22 healthy controls with DCE-MRI of the lumbar spine.RESULTS: A continuous increase in microcirculation parameters amplitude A and exchange rate constant kep reflecting vascular volume and permeability, respectively, was detected from normal controls over MGUS and aMM to sMM. For A and kep, significant differences were found between controls and aMM (P = 0.03 and P = 0.004, respectively) as well as controls and sMM (P = 0.001 and P < 0.001, respectively). Although diffuse microcirculation patterns were found in healthy controls as well as MGUS and MM, a pattern with focal hotspots was exclusively detected in 42.6% of sMM and in 3 MGUS and 3 aMM patients. MGUS and aMM patients with increased microcirculation patterns showed significantly higher bone marrow plasmocytosis compared with patients with a low microcirculation pattern.CONCLUSIONS: Our investigations substantiate the concept of an angiogenic switch from early plasma cell disorders to sMM. Pathologic DCE-MRI findings correlate with adverse prognostic factors and DCE-MRI identifies a distinct group of patients with increased microcirculation parameters in aMM and MGUS patients.
• 2.65

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  Concentric resistance training increases muscle strength without affecting microcirculation.

  Marc-André Weber, Wulf Hildebrandt, Leif Schröder, Ralf Kinscherf, Martin Krix, Peter Bachert, Stefan Delorme, Marco Essig, Hans-Ulrich Kauczor, Holger Krakowski-Roosen

  European journal of radiology. 01/2009;

  PURPOSE: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscl... [more] PURPOSE: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. MATERIALS AND METHODS: Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54+/-9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. RESULTS: The significant (P<0.001) increase in CSA (60+/-16 before vs. 64+/-15cm(2) after training) and in absolute muscle strength (isometric, 146+/-44 vs. 174+/-50Nm; isokinetic, 151+/-53 vs. 174+/-62Nm) demonstrated successful training. Neither capillary density ex vivo (351+/-75 vs. 326+/-62) nor ultrasonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2+/-1.2 vs. 1.1+/-1.1ml/min/100g; blood flow velocity, 0.49+/-0.44 vs. 0.52+/-0.74mms(-1)). Also, the intensities of high-energy phosphates phosphocreatine and beta-adenosintriphosphate were not different after training within the skeletal muscle at rest (beta-ATP/phosphocreatine, 0.29+/-0.06 vs. 0.28+/-0.04). CONCLUSION: The significant increase in muscle size and strength in response to concentric isokinetic and isometric resistance training occurs without an increase in the in vivo microcirculation of the skeletal muscles at rest.