Ernst J. Rummeny

Monitoring radiation-induced changes in bone marrow histopathology with ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI.

The purpose of this study was to monitor radiation‐induced alterations of the blood‐bone marrow barrier (BMB) and the reticuloendothelial system (RES) with AMI‐227‐enhanced magnetic resonance imaging (MRI). Twenty New Zealand white rabbits (n = 10 following total body irradiation and n = 10 controls) underwent AMI‐227‐enhanced MRI. Pulse sequences included dynamic fast low‐angle shot (FLASH; TR/TE 50/4 msec, flip angle 60°) MRI and static T1‐ and T2‐weighted spin‐echo (SE) and turbo‐SE sequences of the lumbar spine and sacrum. Bone marrow enhancement was quantified as Δ signal intensity (SI) (%) = |[(SIpost ‐ SIpre)/SIpre] × 100%| and compared with histopathology, including iron stains and electron microscopy. Dynamic bone marrow ΔSI (%) data steadily increased up to 10–15 minutes after AMI‐227 administration, while blood ΔSI (%) data stayed nearly constant, histologically corresponding to iron oxide leakage into the bone marrow interstitium. This bone marrow contrast enhancement increased significantly following irradiation, corresponding to alterations of the endothelial lining of the bone marrow sinusoids. Late postcontrast images exhibited a significant positive T1 enhancement and negative T2 enhancement of the normal bone marrow, which further increased with irradiation due to increased RES activity. Irradiation‐induced changes in bone marrow physiology could be reliably assessed with AMI‐227‐enhanced MRI. J. Magn. Reson. Imaging 1999;9:643–652, 1999.

Neue MR-Kontrastmittel in der LeberdiagnostikErste klinische Ergebnisse mit hepatobiliärem Eovist® (Gadolinium-EOB-DTPA) und RES-spezifischem Resovist® (SH U 555 A)

ZusammenfassungIn der vorliegenden Arbeit werden erste klinische Ergebnisse (66 Patienten) der für die Leberbildgebung entwickelten Kontrastmittel Resovist® und Eovist® vorgestellt. Es wurden Sicherheitsaspekte, Dosierungsfragen und die optimale Untersuchungstechnik am Beispiel fokaler Leberläsionen untersucht. Beide „leberspezifischen“ Kontrastmittel zeigten bei guter Verträglichkeit eine Verbesserung des Nachweises fokaler Leberläsionen. Die Untersuchung mit Resovist® kann bereits 10 min nach der Kontrastmittelinjektion erfolgen. Mit einer Dosis von 8 μmol Fe/kg Körpergewicht konnte eine ausreichender Tumor-Leber-Kontrast erzielt werden. Da Eovist® zusätzlich im Bolus injiziert werden kann, ergeben sich neben dem Nachweis fokaler Leberläsionen Möglichkeiten der Charakterisierung durch Analyse der Perfusionsmuster. Atemgehaltene T 1-gewichtete FLASH-Sequenzen waren sonstigen T 1-gewichteten Sequenzen ohne und mit Fettgesättigung überlegen.SummaryThe purpose of this work is to describe our initial clinical experience (in 66 patients) with Resovist and Eovist, two new liver-specific MR contrast agents. We focus our report on safety aspects, dose finding, and optimization of technical parameters. Both contrast agents were well tolerated and improved the detectability of focal liver lesions. With Resovist, postcontrast MRI may be started as early as 10 min following injection. The dose of 8 μmol Fe/kg bodyweight was sufficient to achieve diagnostic tumor-liver contrast levels. Since Eovist can also be administered as a bolus, dynamic enhance- ment patterns may be studied for tumor characterization as well. Breath-hold T 1-weighted FLASH images were superior to other T 1-weighted techniques with and without fat saturation.

Die Wertigkeit der 3-Phasen-Spiral-CT und der Magnetresonanztomographie in der präoperativen Diagnostik des Pankreaskarzinoms

ZusammenfassungDas Ziel der vorliegenden Untersuchung an 28 Patienten war die Bestimmung der Wertigkeit der Spiralcomputertomographie (Spiral-CT) und der Magnetresonanztomographie (MRT) im präoperativen Staging des Pankreaskarzinoms. Dazu wurde vergleichend die Infiltration peripankreatischer arterieller und venöser Gefäßstrukturen analysiert. Die Befunde wurden mit dem Ergebnis der Laparotomie korreliert, der alle Patienten unabhängig von den Ergebnissen der Spiral-CT und der MRT unterzogen wurden. Zur präoperativen Bestimmung der lokalen Ausdehnung von Pankreaskarzinomen und damit der Operabilität sind sowohl die 3-Phasen-Spiral-CT und die MRT (± Gadolinium-DTPA) gleichermaßen geeignete Untersuchungsmethoden. Insbesondere können beide Untersuchungsverfahren die Infiltration benachbarter vaskulärer Strukturen präoperativ mit hoher Genauigkeit nachweisen und somit die Planung des operativen Vorgehens beeinflussen.SummaryThe purpose of this study was to assess the role of spiral computed tomography (SCT) and magnetic resonance imaging (MRI) in the preoperative work-up of patients with pancreatic carcinoma, regarding local resectability and vascular involvement. Methods and materials: A total of 28 patients (19 men and 9 women; mean age 58 years) with known or highly suspected carcinoma of the pancreas were included in this study. All patients prospectively underwent MRI (± gadolinium-DTPA) and SCT (3-phase examination) as preoperative diagnostic imaging studies, and laparotomy was carried out within 7 days, irrespective of the MRI or SCT findings. SCT and MR studies were reviewed independently by two radiologists, without knowing the results of the surgical exploration. Standardized image analysis was correlated with findings at laparatomy. Results: Laparotomy identified 10 patients to be suitable for surgical resection and 18 pancreatic carcinomas to be unresectable. In 17 of 18 non-resectable carcinomas MRI and SCT were able to obtain correct information about unresectability (sensitivity 94 %), in 7 (MRI), resp. 8 (SCT) carcinomas were correctly considered to be resectable (sensitivity 70 % for MRI and 80 % for SCT). The presence of vascular involvement was depicted by SCT with a sensitivity of 82–100 % and 62–100 % by MRI. The specificity varied between 85–100 % for SCT and 77–100 % for MRI. Conclusion: Both MRI and SCT are good techniques for the preoperative work-up of pancreatic carcinomas in order to obtain a correct assessment of local resectability.

Structural analysis of human proximal femur for the prediction of biomechanical strength in vitro: the locally adapted scaling vector method

We introduce an image structure analysis technique suitable in cases where anisotropy plays an important role. The so-called Locally Adapted Scaling Vector Method (LSVM) comprises two steps. First, a procedure to estimate the local main orientation at every point of the image is applied. These orientations are then incorporated in a structure characterization procedure. We apply this methodology to High Resolution Magnetic Resonance Images (HRMRI) of human proximal femoral specimens IN VITRO. We extract a 3D local texture measure to establish correlations with the biomechanical properties of bone specimens quantified via the bone maximum compressive strength. The purpose is to compare our results with the prediction of bone strength using similar isotropic texture measures, bone mineral density, and standard 2D morphometric parameters. Our findings suggest that anisotropic texture measures are superior in cases where directional properties are relevant.

[New MR contrast media in liver diagnosis. Initial clinical results with hepatobiliary Eovist (gadolinium-EOB-DTPA) and RES-specific Resovist (SH U 555 A)].

ZusammenfassungIn der vorliegenden Arbeit werden erste klinische Ergebnisse (66 Patienten) der für die Leberbildgebung entwickelten Kontrastmittel Resovist® und Eovist® vorgestellt. Es wurden Sicherheitsaspekte, Dosierungsfragen und die optimale Untersuchungstechnik am Beispiel fokaler Leberläsionen untersucht. Beide „leberspezifischen“ Kontrastmittel zeigten bei guter Verträglichkeit eine Verbesserung des Nachweises fokaler Leberläsionen. Die Untersuchung mit Resovist® kann bereits 10 min nach der Kontrastmittelinjektion erfolgen. Mit einer Dosis von 8 μmol Fe/kg Körpergewicht konnte eine ausreichender Tumor-Leber-Kontrast erzielt werden. Da Eovist® zusätzlich im Bolus injiziert werden kann, ergeben sich neben dem Nachweis fokaler Leberläsionen Möglichkeiten der Charakterisierung durch Analyse der Perfusionsmuster. Atemgehaltene T 1-gewichtete FLASH-Sequenzen waren sonstigen T 1-gewichteten Sequenzen ohne und mit Fettgesättigung überlegen.SummaryThe purpose of this work is to describe our initial clinical experience (in 66 patients) with Resovist and Eovist, two new liver-specific MR contrast agents. We focus our report on safety aspects, dose finding, and optimization of technical parameters. Both contrast agents were well tolerated and improved the detectability of focal liver lesions. With Resovist, postcontrast MRI may be started as early as 10 min following injection. The dose of 8 μmol Fe/kg bodyweight was sufficient to achieve diagnostic tumor-liver contrast levels. Since Eovist can also be administered as a bolus, dynamic enhance- ment patterns may be studied for tumor characterization as well. Breath-hold T 1-weighted FLASH images were superior to other T 1-weighted techniques with and without fat saturation.

Improving the textural characterization of trabecular bone structure to quantify its changes: the locally adapted scaling vector method

We extend the recently introduced scaling vector method (SVM) to improve the textural characterization of oriented trabecular bone structures in the context of osteoporosis. Using the concept of scaling vectors one obtains non-linear structural information from data sets, which can account for global anisotropies. In this work we present a method which allows us to determine the local directionalities in images by using scaling vectors. Thus it becomes possible to better account for local anisotropies and to implement this knowledge in the calculation of the scaling properties of the image. By applying this adaptive technique, a refined quantification of the image structure is possible: we test and evaluate our new method using realistic two-dimensional simulations of bone structures, which model the effect of osteoblasts and osteoclasts on the local change of relative bone density. The partial differential equations involved in the model are solved numerically using cellular automata (CA). Different realizations with slightly varying control parameters are considered. Our results show that even small changes in the trabecular structures, which are induced by variation of a control parameters of the system, become discernible by applying the locally adapted scaling vector method. The results are superior to those obtained by isotropic and/or bulk measures. These findings may be especially important for monitoring the treatment of patients, where the early recognition of (drug-induced) changes in the trabecular structure is crucial.

Comparison and combination of scaling index method and Minkowski Functionals in the analysis of high resolution magnetic resonance images of the distal radius in vitro

High resolution magnetic resonance (HRMR) imaging can reveal major characteristics of trabecular bone. The quantification of this trabecular micro architecture can be useful for better understanding the progression of osteoporosis and improve its diagnosis. In the present work we applied the scaling index method (SIM) and Minkowski Functionals (MF) for analysing tomographic images of distal radius specimens in vitro. For both methods, the correlation with the maximum compressive strength (MCS) as determined in a biomechanical test and the diagnostic performance with regard to the spine fracture status were calculated. Both local SIM and global MF methods showed significantly better results compared to bone mineral density measured by quantitative computed tomography. The receiver operating characteristic analysis for differentiating fractured and non-fractured subjects revealed area under the curve (AUC) values of 0.716 for BMD, 0.897 for SIM and 0.911 for MF. The correlation coefficients with MCS were 0.6771 for BMD, 0.843 for SIM and 0.772 for MF. We simulated the effect of perturbations, namely noise effects and intensity variations. Overall, MF method was more sensitive to noise than SIM. A combination of SIM and MF methods could, however, increase AUC values from 0.85 to 0.89 and correlation coefficients from 0.71 to 0.82. In conclusion, local SIM and global MF techniques can successfully be applied for analysing HRMR image data. Since these methods are complementary, their combination offers a new possibility of describing MR images of the trabecular bone, especially noisy ones.

Application of the scaling index method to µ-CT images of human trabecular bone for the characterization of biomechanical strength

Osteoporosis is a metabolic bone disorder characterized by the loss of bone mineral density (BMD) and the deterioration of the bone micro-architecture. Rarefied bone structures are more susceptible to fractures which are the worst complications of osteoporosis. Here, we apply a structure characterization method, namely the Scaling Index Method, to micro-computed tomographic (&mgr;-CT) images of the distal radius and extract 3D nonlinear structure measures to assess the biomechanical properties of trabecular bone. Biomechanical properties were quantified by the maximum compressive strength (MCS) obtained in a biomechanical test and bone mineral density (BMD) was calculated using dual X-ray absorptiometry (DXA). &mgr;-CT images allow for the application of two different modalities of the SIM which differ in the dimensional embedding of the image. Both representations lead to similar correlation coefficients with MCS which are significantly better than the ones obtained using standard 3D morphometric parameters and comparable to the result given by BMD. The analysis of &mgr;-CT images based on the SIM allows for a sharp distinction of the different structural elements which compose the trabecular bone network.

Performance of linear and nonlinear texture measures in 2D and 3D for monitoring architectural changes in osteoporosis using computer-generated models of trabecular bone

Osteoporosis is a metabolic bone disease leading to de-mineralization and increased risk of fracture. The two major factors that determine the biomechanical competence of bone are the degree of mineralization and the micro-architectural integrity. Today, modern imaging modalities (high resolution MRI, micro-CT) are capable of depicting structural details of trabecular bone tissue. From the image data, structural properties obtained by quantitative measures are analysed with respect to the presence of osteoporotic fractures of the spine (in-vivo) or correlated with biomechanical strength as derived from destructive testing (in-vitro). Fairly well established are linear structural measures in 2D that are originally adopted from standard histo-morphometry. Recently, non-linear techniques in 2D and 3D based on the scaling index method (SIM), the standard Hough transform (SHT), and the Minkowski Functionals (MF) have been introduced, which show excellent performance in predicting bone strength and fracture risk. However, little is known about the performance of the various parameters with respect to monitoring structural changes due to progression of osteoporosis or as a result of medical treatment. In this contribution, we generate models of trabecular bone with pre-defined structural properties which are exposed to simulated osteoclastic activity. We apply linear and non-linear texture measures to the models and analyse their performance with respect to detecting architectural changes. This study demonstrates, that the texture measures are capable of monitoring structural changes of complex model data. The diagnostic potential varies for the different parameters and is found to depend on the topological composition of the model and initial “bone density”. In our models, non-linear texture measures tend to react more sensitively to small structural changes than linear measures. Best performance is observed for the 3rd and 4th Minkowski Functionals and for the scaling index method.

Röntgen-Phasenkontrast: Grundlagen, Potenzial und Fortschritte in der klinischen Translation

ZusammenfassungVor mehr als 100xa0Jahren entdeckte Max von Laue in München, dass Röntgenstrahlung nicht nur als Röntgenquanten im Teilchenbild interpretiert werden kann, sondern ebenso einen Wellencharakter aufweist. Diese Eigenschaft wird mittlerweile auch schon lange in der Grundlagenforschung eingesetzt (z.xa0B. in der Kristallographie zur Strukturbestimmung von Proteinen), hatte bisher jedoch keine Anwendung in der medizinischen Bildgebung. In den letzten 10xa0Jahren allerdings konnten in der vorklinischen Forschung sehr große technologische Fortschritte erzielt werden, die eine Nutzung dieses Wellencharakters von Röntgenlicht auch für die medizinische Bildgebung möglich machen. Diese neuartigen Radiographie-Verfahren, die sog.xa0Phasenkontrast- und Dunkelfeldbildgebung, bergen ein großes Potenzial für eine deutliche Verbesserung der Röntgenbildgebung und somit auch der Diagnose von wichtigen Krankheiten. Dieser Artikel zeigt die Grundprinzipien dieser neuen Verfahren auf, fasst exemplarisch die bereits erreichten vorklinischen Forschungsergebnisse an verschiedenen Organen zusammen und zeigt das Potenzial für die zukünftige klinische Nutzung in Radiographie und Computertomographie auf.AbstractMore than 100 years ago Max von Laue in Munich discovered that X‑rays can be interpreted not only as X‑ray quanta in axa0particle picture, but also show a wave character. This property has been used for a long time in basic research (e.g. in crystallography for determining the structure of proteins), but so far has had no application in medical imaging. In the last 10xa0years, however, very impressive technological progress could be made in preclinical research, which also makes the utilization of the wave character of X‑ray light possible for medical imaging. These novel radiography procedures, so-called phase-contrast and dark-field imaging, have a great potential for a pronounced improvement in X‑ray imaging and therefore, also the diagnosis of important diseases. This article describes the basic principles of these novel procedures, summarizes the preclinical research results already achieved exemplified by various organs and shows the potential for future clinical utilization in radiography and computed tomography.More than 100 years ago Max von Laue in Munich discovered that X‑rays can be interpreted not only as X‑ray quanta in axa0particle picture, but also show a wave character. This property has been used for a long time in basic research (e.g. in crystallography for determining the structure of proteins), but so far has had no application in medical imaging. In the last 10xa0years, however, very impressive technological progress could be made in preclinical research, which also makes the utilization of the wave character of X‑ray light possible for medical imaging. These novel radiography procedures, so-called phase-contrast and dark-field imaging, have a great potential for a pronounced improvement in X‑ray imaging and therefore, also the diagnosis of important diseases. This article describes the basic principles of these novel procedures, summarizes the preclinical research results already achieved exemplified by various organs and shows the potential for future clinical utilization in radiography and computed tomography.