J. Griebel

Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series.

The purpose of this study was to quantify microcirculation and microvasculature in breast lesions by pharmacokinetic analysis of Gd‐DTPA‐enhanced MRI series. Strongly T1‐weighted MR images were acquired in 18 patients with breast lesions using a saturation‐recovery‐TurboFLASH sequence. Concentration‐time courses were determined for blood, pectoral muscle, and breast masses and subsequently analyzed by a two‐compartment model to estimate plasma flow and the capillary transfer coefficient per unit of plasma volume (F/VP, KPS/VP) as well as fractional volumes of the plasma and interstitial space (fP, fI). Tissue parameters determined for pectoral muscle (fP = 0.04 ± 0.01, fI = 0.09 ± 0.01, F/VP = 2.4 ± 1.3 min‐1, and KPS/VP = 1.2 ± 0.5 min‐1) and 10 histologically proven carcinomas (fP = 0.20 ± 0.07, fI = 0.34 ± 0.16, F/VP = 2.4 ± 0.7 min‐1, and KPS/VP = 0.86 ± 0.62 min‐1) agreed reasonable well with literature data. Best separation between malignant and benign lesions was obtained by the ratio KPS/F (0.35 ± 0.17 vs. 1.23 ± 0.65). The functional imaging technique presented appears promising to quantitatively characterize tumor pathophysiology. Its impact on diagnosis and therapy management of breast tumors, however, has to be evaluated in larger patient studies. Magn Reson Med 52:420–429, 2004.

Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma

PURPOSE The aim of our study was to correlate perfusion indices and apparent diffusion coefficients with therapy outcome after chemoradiation. METHODS AND MATERIALS In 34 patients with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation, pretherapeutic perfusion indices and apparent diffusion coefficients were obtained by dynamic or diffusion-weighted magnetic resonance imaging. Therapy response was defined if the pathologic observation revealed no invasion into the perirectal fat after chemoradiation. RESULTS In 18 patients, a response and in 16, no response was observed. Statistically significant differences were found for the mean perfusion index (p < 0.001; 7.5 +/- 1.5 mL/min/100 g vs. 10.7 +/- 2.7 mL/min/100 g) and for the intratumoral cumulative fraction of pixels with perfusion-indices > 12 mL/min/100 g (p < 0.001, 3.7 +/- 4.0% vs. 24.7 +/- 17.9%). A three-way ANOVA resulted in significant effects for therapy responder/nonresponder (p < 0.001) and for apparent diffusion coefficient and the individual patients. CONCLUSION Perfusion indices and apparent diffusion coefficients inside the tumor region seem to be of predictive value for therapy outcome of preoperative therapy in patients with primary rectal carcinoma. Higher parameter levels in the nonresponding group could be explained by increased shunt flow or increased angiogenic activity in aggressive tumor cell clusters resulting in reduced nutrients supply and higher fraction of intratumoral necrosis respectively.

Diffusion-weighted magnetic resonance imaging for monitoring diffusion changes in rectal carcinoma during combined, preoperative chemoradiation: preliminary results of a prospective study.

PURPOSE To evaluate the clinical value of diffusion-weighted magnetic resonance imaging (DW-MRI) to monitor response of primary carcinoma of the rectum to preoperative chemoradiation by measuring tumor apparent diffusion coefficient (ADC). MATERIALS AND METHODS Diffusion data of nine patients undergoing preoperative combined chemoradiation for clinical staged T3, N(0-2), M(0) carcinoma of the rectum were analyzed. Diffusion-weighted echo-planar MR images were obtained prior to and at specified intervals during chemoradiation and ADCs calculated from acquired tumor images. RESULTS Comparison of mean ADC and cumulative radiation dose showed a significant decrease of mean ADC at the 2nd (P = 0.028), 3rd (P = 0.012), and 4th (P = 0.008) weeks of treatment. Cytotoxic edema and fibrosis were considered as reasons for ADC decrease. CONCLUSION This study demonstrated tumor ADC changes via detection of therapy-induced alterations in tumor water mobility. Our results indicate that diffusion-weighted imaging may be a valuable clinical tool to diagnose the early stage of radiation-induced fibrosis.

Preliminary Results on the Influence of Chemoradiation on Apparent Diffusion Coefficients of Primary Rectal Carcinoma Measured by Magnetic Resonance Imaging

Purpose:To study changes of the apparent diffusion coefficient (ADC) measured by magnetic resonance imaging (MRI) in patients with primary rectal carcinoma during a course of combined chemoradiation.Patients and Methods:Diffusion-weighted echo-planar imaging at 1.5 T was performed in patients (n = 8) with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation. Mean tumor ADC values and ADC histograms were determined and compared weekly during the course of therapy. Surgical resection of the tumors enabled a correlation of ADC values with the pathologic classification.Results:In four patients tumor T-downstaging (ypT0–2) was observed, and in four patients no downstaging (ypT3) was seen. In all patients, ADC values were higher before onset of chemoradiation therapy compared to the end of chemoradiation. Separating the patients into two groups, a significant increase in ADC value during week 1 of therapy, followed by a steady decrease, was found for the therapy-responder group. In the nonresponder group, no initial increase of ADC values was observed. After the 1st week of therapy, ADC values were significantly lower in the nonresponder group during the remaining duration of therapy.Conclusion:With these preliminary results it could be shown that MR diffusion imaging is able to detect individual changes of tumor ADC values during the course of combined chemoradiation reflecting biological changes within the tumor tissue. Further studies will be necessary to prove the possible value of totally noninvasive ADC imaging on predicting therapy outcome.Ziel:Untersuchung von Änderungen des mittels diffusionsgewichteter Magnetresonanztomographie (DMRT) gemessenen Diffusionskoeffizienten (ADC) in primären Rektumkarzinomen während kombinierter Radiochemotherapie.Patienten und Methodik:Diffusionsgewichtete echoplanare Bildgebung wurde an einem 1,5-T-MR-Gerät bei Patienten (n = 8) mit primären Rektumkarzinomen (cT3) während kombinierter Radiochemotherapie durchgeführt. Mittlere Tumor-ADC-Werte und ADC-Histogramme wurden im Verlauf der Therapie wöchentlich erfasst und verglichen. Die sich an die Therapie anschließende chirurgische Resektion des Tumors ermöglichte eine Korrelation der ADC-Werte mit der pathologischen Klassifikation.Ergebnisse:Bei vier Patienten wurde eine Verbesserung des Tumorstadiums (ypT0–2) beobachtet, und bei vier Patienten war keine Verbesserung des Tumorstadiums (ypT3) feststellbar. Zwischen Anfang und Ende der Therapie kam es bei allen Patienten zu einer signifikanten Abnahme der mittleren ADC-Werte. Für die Patientengruppe mit Verbesserung des Tumorstadiums wurde ein signifikanter Anstieg der ADC-Werte während der 1. Therapiewoche, gefolgt von einer stetigen Abnahme, beobachtet. Für die Patientengruppe ohne Verbesserung des Tumorstadiums wurde keine ADC-Zunahme während der 1. Therapiewoche festgestellt. Nach der 1. Therapiewoche waren die ADC-Werte für die Gruppe ohne Verbesserung des Tumorstadiums signifikant niedriger als für die Gruppe mit Verbesserung des Tumorstadiums.Schlussfolgerung:Diese vorläufigen Ergebnisse zeigen, dass die DMRT in der Lage ist, individuelle Änderungen der ADC-Werte, die biologische Veränderungen im Tumorgewebe widerspiegeln, während kombinierter Radiochemotherapie zu detektieren. Weitere Studien sind notwendig, um die mögliche Bedeutung der vollständig nichtinvasiven DMRT für die Vorhersage des Therapieergebnisses nachzuweisen.

The impact of peak saturation of the arterial input function on quantitative evaluation of dynamic susceptibility contrast-enhanced MR studies.

Purpose The purpose of this work was to investigate systematic errors in dynamic contrast-enhanced MR perfusion studies due to peak saturation of the arterial input function (AIF) and to introduce a simple correction algorithm. Method Computer simulations were performed to evaluate the influence of AIF peak saturation and to demonstrate the effectiveness of the presented correction algorithm. To compare the computer simulations with real MR data, MR perfusion measurements were performed on volunteers. Results The computer simulations show that AIF peak saturation leads to a systematic overestimation of cerebral blood volume (CBV) and cerebral blood flow (CBF) values, which was confirmed by comparing the obtained MR data with PET results. With use of an improved calculation algorithm correcting for AIF peak saturation, a significant improvement of the obtained CBV and CBF values could be demonstrated. Conclusion Our results suggest that AIF peak saturation leads to a significant systematic error in the determination of CBV and CBF values and has necessarily to be taken into account for dynamic contrast-enhanced MR perfusion studies.

Lectin Intravital Perfusion Studies in Tumor-bearing Mice: Micrometer-resolution, Wide-area Mapping of Microvascular Labeling, Distinguishing Efficiently and Inefficiently Perfused Microregions in the Tumor

Intravital lectin perfusion was combined with computer-guided scanning digital microscopy to map the perfused elements of the vasculature in tumor-bearing mice. High-precision composite images (spatial precision 1.3 μm and optical resolution 1.5 μm) were generated to permit exact positioning, reconstruction, analysis, and mapping of entire tumor cross-sections (c. 1 cm in diameter). Collation of these mosaics with nuclear magnetic resonance maps in the same tumor plane identified sites of rapid contrast medium uptake as tumor blood vessels. Digitized imaging after intravital double labeling allowed polychromatic visualization of two different types of mismatched staining. First, simultaneous application of two lectins, each bearing a different fluorochrome, revealed organ-specific differential processing in the microvascular wall. Second, sequential application of two boluses of one lectin, bearing different fluorochromes successively, distinguished between double-labeled microvessels, representing efficiently perfused vascular segments, and single-labeled microvessels, with inefficient or intermittent perfusion. Intravital lectin perfusion images of blood vessels in the vital functional state thus highlighted biologically significant differences in vessel function and served as high-resolution adjuncts to MR imaging.

Radiation exposures of cancer patients from medical X-rays: how relevant are they for individual patients and population exposure?

X-ray procedures have a substantial impact not only on patient care but also on man-made radiation exposure. Since a reliable risk-benefit analysis of medical X-rays can only be performed for diagnosis-related groups of patients, we determined specific exposure data for patients with the ten most common types of cancer. For all patients with the considered cancers undergoing medical X-ray procedures in a maximum-care hospital between 2000 and 2005, patient- and examination-specific data were retrieved from the hospital/radiology information system. From this data, the cumulative 5-year effective dose was estimated for each patient as well as the mean annual effective dose per patient and the mean patient observation time for each cancer site. In total, 151,439 radiographic, fluoroscopic, and CT procedures, carried out in 15,866 cancer patients (age, 62+/-13 years), were evaluated. The mean 5-year cumulative dose varied between 8.6 mSv (prostate cancer) and 68.8 mSv (pancreas cancer). Due to an increasing use of CT scans, the mean annual effective dose per patient increased from 13.6 to 18.2 mSv during the 6-year period. Combining the results obtained in this study for a particular hospital with cancer incidence data for Germany, we estimated that cancer patients having X-ray studies constitute at least 1% of the population but receive more than 10% of the total effective dose related to all medical X-ray procedures performed nationwide per year. A large fraction of this dose is radiobiologically ineffective due to the reduced life expectancy of cancer patients.

Risks and safety aspects related to PET/MR examinations

IntroductionThe introduction of positron emission tomography (PET)/magnetic resonance (MR) systems into medical practice in the foreseeable future may not only lead to a gain in clinical diagnosis compared to PET/computed tomography (CT) imaging due to the superior soft-tissue contrast of the MR technology but can also substantially reduce exposure of patients to ionizing radiation. On the other hand, there are also risks and health effects associated with the use of diagnostic MR devices that have to be considered carefully.ObjectivesThis review article summarizes biophysical and biological aspects, which are of relevance for the assessment of health effects related to the exposure of patients to both ionizing radiation in PET and magnetic and electromagnetic fields in MR. On this basis, some considerations concerning the justification and optimization of PET/MR examinations are presented—as far as this is possible at this very early stage.DiscussionCurrent safety standards do not take into account synergistic effects of ionizing radiation and magnetic and electromagnetic fields. In the light of the developing PET/MR technology, there is an urgent need to investigate this aspect in more detail for exposure levels that will occur at PET/MR systems.

Erfassung und Bewertung der Patientenexposition in der diagnostischen Radiologie und Nuklearmedizin

Zusammenfassung Die regelmasigen Ermittlungen der Patientenexposition in der Strahlendiagnostik durch das Bundesamt fur Strahlenschutz (BfS) besitzen einen hohen Stellenwert bei der Standortbestimmung der radiologischen Qualitats- und Sicherheitskultur sowie der Nutzen-Risiko-Optimierung in Deutschland. Fur das Berichtsjahr 1997 wurde eine mittlere effektive Dosis von 2 ± 0.5 mSv pro Kopf der Bevolkerung durch Rontgenuntersuchungen ermittelt; diesem Dosiswert liegen ca. 136 Millionen Rontgenuntersuchungen zugrunde, entsprechend einer Frequenz von 1,7 Untersuchungen jahrlich pro Kopf der Bevolkerung. Korrespondierend dazu liegt die Exposition durch die Nuklearmedizin bei etwa 0,15 mSv effektiver Dosis pro Kopf der Bevolkerung; die Zahl der nuklearmedizinischen Untersuchungen liegt bei ca. 4 Millionen, entsprechend einer Frequenz von ca. 0,05 Untersuchungen jahrlich pro Kopf der Bevolkerung. Einflussparameter bei der Expositionsermittlung und das Fehlen eines internationalen Konzepts zur Bestimmung der Patientenexposition werden kritisch diskutiert.

Static magnetic fields induce blood flow decrease and platelet adherence in tumor microvessels

Red blood cell flow in capillaries is reduced during exposure to strong static magnetic fields (SMFs). Intratumoral microcirculation is characterized by tortuous microvessels with chaotic architecture and by irregular, sluggish blood flow with unstable rheology.It was the aim of this study to analyze SMF exposure effects on tumor microcirculation with regard to interactions of corpuscular blood components with tumor microvessel walls.In vivo fluorescence microscopy was performed in A-Mel-3 tumors growing in dorsal skinfold chamber preparations of Syrian Golden hamsters. SMFs with varying field strength (< 600 mT) were generated by changing the distance between a strong NdFeB rod magnet and the tissue region of interest.Short-time exposure above a magnetic flux density of about 150 mT resulted in a significant reduction of red blood cell velocity (vRBC) and segmental blood flow in tumor microvessels. At the maximum strength of 587 mT, a reversible reduction of vRBC (~ 40 %) and of functional vessel densitiy (~15 %) was observed.Prolongation of the exposure time from 1 min to up to 3 h resulted in comparable reductions. Microvessel diameters and leukocyte-endothelial cell interactions remained unaffected by SMF exposure. However, in contrast to tumor-free striated muscle controls, exposure at the maximum flux density induced a significant increase in platelet-endothelial cell adherence in a time-dependent manner that was reversible after reducing SMF strength.These reversible changes may have implications for functional measurements of tumor microcirculation by MRI and new therapeutic strategies using strong SMFs.