[Retention of contrast media in the history of radiology : Sequelae of the former use of thorotrast and new challenges]. / Kontrastmittelretention in der Geschichte der Radiologie : Folgen der früheren Thorotrastanwendungen und neue Herausforderungen.

Detection of gadolinium deposits in patients who have repeatedly been administered intravenous gadolinium chelates have given rise to concern regarding the long-term safety of magnetic resonance imaging (MRI) contrast media. Nevertheless, negative long-term clinical effects have not yet been observed. In some publications parallels have been drawn to the sequelae of thorotrast that was formerly used for arterial angiography. In this article the history of thorotrast use is briefly described and in particular why, despite warnings, this substance was used frequently and worldwide. A brief summary of the results of the German Thorotrast Study revealed that high excess rates were only observed for primary malignant liver tumors after a 15-year or longer latency period and to a lesser degree of leukemias, as well as for severe local complications due to paravascular injections, particularly in the neck region. Based on this historical review, we will venture to take stock of the outcome from the "success story" of this contrast agent.

The German Thorotrast Cohort Study: a review and how to get access to the data.

It is well known that exposures like those from (226)Ra, (224)Ra and Thorotrast(®) injections increase the risk of neoplasia in bone marrow and liver. The thorium-based radioactive contrast agent Thorotrast(®) was introduced in 1929 and applied worldwide until the 1950s, especially in angiography and arteriography. Due to the extremely long half-life of several hundred years and the life-long retention of the thorium dioxide particles in the human body, patients suffer lifetime internal exposure. The health effects from the incorporated thorium were investigated in a few cohort studies with a German study being the largest among them. This retrospective cohort study was set up in 1968 with a follow-up until 2004. The study comprises 2326 Thorotrast patients and 1890 patients of a matched control group. For those being alive at the start of the study in 1968 follow-up was done by clinical examinations on a biannual basis. For the others, causes of death were collected in various ways. Additionally, clinical, radiological and biophysical studies of patients were conducted and large efforts were made to best estimate the radiation doses associated with incorporation of the Thorotrast. The aim of this paper is to describe the cohort, important results and some open questions. The data from the German Thorotrast Study are available to other interested researchers. Information can be found at http://storedb.org .

[The medical management of high risk individuals. Experiences with persons exposed to chronic internal irradiation]. / Über den ärztlichen Umgang mit Hochrisikopersonen. Erfahrungen bei Personen mit chronischer interner Strahlenexposition.

The medical management and counseling of persons at high risk due to exposure to chemicals or radiation or due to personal disposition, present an additional challenge for physicians and especially radiologists involved. This article is based on own experiences with patients who had been exposed to Thorotrast. They had been injected with the contrast medium Thorotrast, which was in use world-wide until around 1950. Thorotrast caused a chronic alpha irradiation mainly of the liver (up to 0.4 Gy/a), spleen (1.2 Gy/a) and bone marrow (0.1 Gy/a). For the Thorotrast patients and their physicians the most worrying problem was the risk of primary malignant liver tumors which occurred in more than 20% of the exposed persons, i.e. 100 times more frequently than in a non-exposed control group. The medical and especially radiological experiences with the management of these patients summarize a general aspect of the problem and can be referred to when managing other high risk groups.

[Therapy-induced effects in normal tissue]. / Therapieinduzierte Effekte am Normalgewebe.

More than 50% of cancer patients survive for more than 5 years, owing to modern and effective treatment. Therefore, long-term sequelae of treatment are more frequently seen than in the past. Such effects on normal tissue may both mimic and obscure tumor recurrences. Besides the direct consequences of surgery, tissue damage due to radiation or chemotherapy frequently cause problems in differential diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy changes in bone marrow signals in MRI. The most devastating long-term complications are secondary cancers and leukemia induced by both radiotherapy and chemotherapy.

[Screening in cardiovascular diseases]. / Screening bei Herz- und Gefässkrankheiten.

Cardiovascular disease still ranks number one in the mortality statistics in the industrialized world. In Germany the five most common causes of death are all associated with arteriosclerotic changes of the arterial vasculature. As the treatment often extends over long periods and it can be impossible for patients to work, peripheral arterial occlusive disease (PAOD) constitutes a not inconsiderable economic factor. Thus, screening for arteriosclerotic disease seems to be reasonable, because the potential for influencing arteriosclerotic changes is known to be higher in an early stage of the disease even before symptoms become apparent. Not every case can be cured, but progression can frequently be slowed down. The need for invasive procedures, some of them associated with ionizing radiation, limited the use of imaging of the arterial vasculature for a long time. Noninvasive clinical examinations such as the "ankle brachial index" (ABI) can indicate the presence of PAOD, though exact localization of the pathologic changes is not possible except with imaging methods. In contrast to these, MRI is a noninvasive imaging modality that does not involve ionizing radiation but offers high spatial resolution arterial imaging.

[Comparison of MultiHance and Gadovist for cerebral MR perfusion imaging in healthy volunteers]. / Vergleich von MultiHance((R)) und Gadovist((R)) zur zerebralen MR-Perfusionsmessung bei gesunden Probanden.

To evaluate the weakly protein interacting MR contrast agent MultiHance((R)) and the one-molar agent Gadovist((R)) for cerebral perfusion MR imaging, a randomized intraindividual study was conducted in 12 healthy male volunteers. Perfusion-MRI was performed with single and double dose of each contrast agent on a 1.5T MR system using a gradient-echo EPI sequence. The imaging parameters, slice positioning and contrast media application were standardized. For the quantitative assessment rCBV and rCBF measurements of gray and white matter were performed. Additionally, the percentage of signal drop and the full width half maximum (FWHM) of ROI signal time curves were quantified. In a qualitative analysis the image quality of the rCBV and rCBF maps were assessed. Single dosage of the used new contrast agents was sufficient to achieve high quality perfusion maps. The susceptibility effect, described by percentage of signal loss (Gadovist((R)): 29.4% vs. MultiHance((R)): 28.3%) and the FWHM (Gadovist((R)): 6.4 s vs. Multihance((R)): 7.0 s) were not different between the agents for single dose. The one molar MR contrast agent Gadovist((R)) has no advantages over MultiHance((R)), a MR contrast agent with a higher relaxivity in perfusion MRI. Both agents allow the calculation of high quality perfusion maps at a dosage of 0.1 mmol/kg bw with physiologic absolute values for regional CBV and CBF. The susceptibility effect is comparable for both agents and stronger than with conventional MR contrast media.

Cerebral arteriovenous malformations: morphologic evaluation by ultrashort 3D gadolinium-enhanced MR angiography.

The purpose of this study was to evaluate the usefulness of a new ultrashort contrast-enhanced (CE) MR angiography (MRA) for the morphologic evaluation of cerebral arteriovenous malformations (AVMs). The method was compared with conventional X-ray digital subtraction angiography (DSA) and time-of-flight (TOF) MRA in 22 patients to assess the angioarchitecture of the malformations which is essential for treatment planning and follow-up. Two experienced MR readers independently evaluated both techniques with regard to the assessment of feeding arteries, AVM nidus, and venous drainage patterns. Contrast-enhanced MRA was able to detect all AVMs seen on DSA, whereas the TOF MRA failed in 1 patient with a very small AVM. In the assessment of the different vessel components of the AVM there was no difference for the detection and delineation of feeding arteries and the AVM. The venous drainage patterns could always be clearly delineated in the CE MRA, whereas TOF MRA could demonstrate the exact venous drainage in only 9 patients. Contrast-enhanced MRA was found to be superior to conventional TOF MRA in the assessment of the angioarchitecture of cerebral AVMs especially regarding the assessment of the venous drainage patterns. The superiority is supported by the improved vessel-to-background contrast and contrast-to-noise ratios. The major limitations of this new technique consist of a low spatial resolution at the used time resolution which can be improved by further sequence modifications. Contrast-enhanced MRA is thus an important additional imaging technique for treatment planning and follow-up of AVMs.

[Successful long-term treatment of multiple metastases from renal cell carcinoma: combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery]. / Erfolgreiche Langzeitbehandlung bei multiplen Hirnmetastasen eines Nierenzellkarzinoms Kombination von stereotaktischer Einzeitkonvergenzbestrahlung und Operation.

The case of a patient suffering from renal cell carcinoma and recurrent brain metastases shows how the survival period can be significantly prolonged by a combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery. This 58-year-old man's left kidney was completely excised because of a renal cell carcinoma. After 18 months and 25 months, respectively, a right frontal brain metastasis was operated on. In the next 7 years, biannual MRI checks were carried out which successively showed five different brain metastases, each of which was immediately subjected to single-dose stereotactic irradiation (median dosage: 20 Gy prescribed to the 80% isodose). In the following 2 years, operations were carried out on two metastases which could not be treated by radiation because of their considerable size and partial compression of the ventricle. In the next 3 years, four more brain metastases were subjected to single-dose stereotactic irradiation. There were no metastases in the other organs. At present, the patient is in good clinical condition and mobile. A negative prognosis is usually delivered for patients suffering from renal cell carcinoma and brain metastasis. However, in individual cases, the survival period can be significantly prolonged by regular MRI examinations and a combination of neurosurgery and single-dose stereotactic irradiation.

Differentiation of radiation necrosis from tumor progression using proton magnetic resonance spectroscopy.

We report on a young woman who was treated by stereotactic radiotherapy for recurrence of an initially resected low-grade astrocytoma. MRI follow-up examination 7 months after radiotherapy showed a gadolinium-DTPA-enhancing mass lesion indicative of high-grade tumor progression. This assumption was also supported by positron emission tomography with [2-18F]fluoro-2-deoxy-D-glucose (FDG-PET). In contrast, proton MR spectroscopy (1H-MRS) indicated radiation necrosis, which was confirmed histopathologically in surgical specimens. Subsequent follow-up examinations up to 19 months after surgery showed no evidence of tumor recurrence.

Postoperative fluid-attenuated inversion recovery MR imaging of cerebral gliomas: initial results.

Fluid-attenuated inversion-recovery (FLAIR) imaging has shown to be a valuable imaging modality in the assessment of intra-axial brain tumors; however, no data are available about the role of this technique in the clinically important postoperative stage. The purpose of this study was to evaluate the diagnostic potential of FLAIR MR imaging in residual tumor after surgical resection of cerebral gliomas. Fifteen patients with residual cerebral gliomas were examined within the first 18 days after partial surgical resection of cerebral gliomas. The imaging protocol included T1-weighted spin echo, T2- and proton-density-weighted fast spin echo, and FLAIR imaging with identical slice parameters. T1 and FLAIR were repeated after contrast media application. Detection and delineation of residual tumor were the primary parameters of the image analysis. Additionally, the influence of image artifacts on the image interpretation was assessed. On FLAIR images residual signal abnormalities at the border of the resection cavities were observed in all patients, whereas T2- and T1-weighted images present residual abnormalities in 13 of 15 and 10 of 15 patients, respectively. The FLAIR imaging was found to be superior to conventional imaging sequences in the delineation of these changes and comparable to contrast enhanced T1-weighted imaging in the delineation of residual enhancing lesions. Because of protein cell components and blood byproducts within the resection cavity, FLAIR imaging was unable to suppress the cerebrospinal fluid (CSF) in 4 patients. After the decomposition of proteins and blood, CSF could again be completely suppressed and residual or recurrent tumors were clearly identified. Our preliminary study has shown that FLAIR may be a valuable diagnostic modality in the early postoperative MR imaging after resection of cerebral gliomas due to its better delineation of residual pathologic signal at the border of the resection cavity. It should therefore be integrated into the early and/or intraoperative MR imaging protocol.

Proton MR spectroscopic evaluation of suspicious brain lesions after stereotactic radiotherapy.

BACKGROUND AND PURPOSE: The radiologic assessment of suspicious brain lesions after stereotactic radiotherapy of brain tumors is difficult. The purpose of our study was to define parameters from single-voxel proton MR spectroscopy that provide a probability measure for differentiating neoplastic from radiation-induced, nonneoplastic lesions. METHODS: Seventy-two lesions in 56 patients were examined using a combined MR imaging and MR spectroscopy protocol (point-resolved spectroscopy, TE = 135 ms). Signal intensities of cholines, creatines, N-acetyl aspartate, and the presence of lactate and lipid resonances were correlated to final diagnoses established by clinical and MR imaging follow-up, positron emission tomography studies, or biopsy/surgery. Statistical analysis was performed using the t test, linear discriminant analysis, and k nearest-neighbor method. RESULTS: Significantly increased signal intensity ratios I(tCho)/I(tCr) (P <.0001) and I(tCho)/I(NAA) (P <.0001) were observed in neoplastic (n = 34) compared with nonneoplastic lesions (n = 32) and contralateral normal brain (n = 33). Analysis of I(tCho)/I(tCr) and I(tCho)/I(NAA) data yielded correct retrospective classification as neoplastic and nonneoplastic in 82% and 81% of the lesions, respectively. Neither I(NAA)/I(tCr) nor signal intensitities of lactate or lipids were useful for differential diagnosis. CONCLUSION: Metabolic information provided by proton MR spectroscopy is useful for the differentiation of neoplastic and nonneoplastic brain lesions after stereotactic radiotherapy of brain tumors.

Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging.

The aim of our study was to investigate the quantitative microcirculation parameters amplitude A (hypothetical intravascular volume) and exchange rate constant k(21) (hypothetical vascular permeability) by contrast-enhanced dynamic magnetic resonance imaging (dMRI) as markers of angiogenesis in multiple myeloma (MM). Therefore lumbar spine and spina iliaca superior posterior of 16 normal controls and 41 patients with active MM were assessed using a dMRI protocol with a pump controlled bolus infusion of Gadolinium-DTPA. Pharmacokinetic parameters, amplitude A and exchange rate constant k(21) were calculated according to a 2-compartment model. Color-coded parameter images were generated from pharmacokinetic data analysis and superimposed onto the conventional MR images. Amplitude A and k(21) parameters were significantly increased in patients with MM compared with controls (p = 0.001; median A(ctr), 0.2 [range, 0.09-0.4]; median A(MM), 0.93 [range, 0.2-2.2]; median k(21ctr), 0.09 min(-1) [range, 0.03-0.9]; median k(21MM), 4.58 [range, 0.22-23.8]). Within the group of MM patients the pattern of color-coded parameter images were found to be either of "diffuse" (n = 13, 31%) or "focal" (n = 28, 69%) type of distribution of microcirculation. Comparison of amplitude A in patients with "focal" vs. "diffuse" pattern of the pharmacokinetic maps revealed a significant increase in the median of amplitude A in the "focal" group. Amplitude A values allowed a classification of patients according to severe osteolytic bone involvement (p = 0.023) with the best cutoff value of 0.7 for amplitude A. Downmodulation of amplitude A was observed in a MM patient treated with standard VAD chemotherapy. Our data demonstrate that dMRI is a novel imaging technique for the detection and monitoring of MM bone lesions. It provides independent evidence for angiogenesis in MM.

Transient enlargement of contrast uptake on MRI after linear accelerator (linac) stereotactic radiosurgery for brain metastases.

PURPOSE/OBJECTIVE: With the increasing number of patients successfully treated with stereotactic radiosurgery for brain metastases, decision making after therapy based on follow-up imaging findings becomes more and more important. Magnetic resonance imaging (MRI) is the most sensitive means for follow-up studies. The objective of this study was to investigate the treatment outcome of our radiosurgery program and to describe the response of brain metastases to contrast-enhanced MRI after linear accelerator (linac) stereotactic radiosurgery and identify factors to distinguish among local control and local failure. METHODS AND MATERIALS: Using serial MRI, we followed the course of 87 brain metastases in 48 consecutive patients treated between September 1996 and November 1997 with linac-based radiosurgery with 15-MV photons. Treatment planning was performed on an MR data cube. For spherical metastases, radiosurgery was delivered using a 9 noncoplanar arc technique with circular-shaped collimators. For irregularly shaped targets, radiosurgery was delivered using a manually driven multi-leaf collimator with a leaf width of 1.5 mm projected to the isocenter. Median radiosurgery dose was 20 Gy prescribed to the 80% isodose. Together with whole brain radiotherapy (20 x 2 Gy, 5/w), a median radiosurgical dose of 15 Gy was delivered. Median follow-up was 8 (range 2--36) months. Factors influencing local control and survival rates were analyzed with respect to MRI response, and Kaplan-Meier curves were calculated. RESULTS: Actuarial local tumor control was 91% at one and two years. Patient survival at one and two years was 30% and 18%. Median survival was 9 months. During follow-up in 70 (81%) of the 87 treated metastases, the contrast-enhancing volumes on T1W images were stable or disappeared partly or completely. A transient enlargement of contrast-enhancing volumes was observed in 11 (12%) of the 87 lesions treated, while a progressive enlargement due to local treatment failure was observed in 6 (7%) of the 87 treated metastases. Younger age, early contrast onset after radiosurgery, and previous chemotherapy were associated with this transient enlargement of contrast-enhancing lesion volume. CONCLUSIONS: Linac-based radiosurgery is an effective, noninvasive, and safe treatment option for patients with brain metastases. A marked enlargement of the contrast-enhancing volume on T(1)-weighted MR images after radiosurgery is a sensitive predictor for, but not equivalent with, local failure. In as many as two-thirds of the cases with contrast enlargement in MRI follow-up, the contrast enlargement is transient with no need for further treatment. While some MRI findings are more likely if transient enlargement is present, a clear decision cannot be made based on MRI, and ultimately the clinical status dictates further action.

[Imaging the smallest tumor vessels using color Doppler ultrasound in an experiment]. / Darstellbarkeit kleinster Tumorgefässe mit Hilfe der Farbdopplersonographie im Experiment.

PURPOSE: We present an experimental, statistical approach to estimate the size required for small vessels to become detectable with color Doppler sonography. MATERIALS AND METHODS: A murine experimental tumor was examined with color Doppler sonography after injection of 1.5 ml of the contrast medium Levovist. Histologically, we measured vessel diameters inside the tumor as well as other, clearly identifiable locations. RESULTS: With color Doppler at a transmit frequency of 7 MHz, vessels were only detected in the tumor's environment, but not inside. From the 95% quantiles of the vessel diameter distribution found histologically, we estimate that vessels 80-140 microns in diameter or above may be detectable with color Doppler sonography, while vessels 40 microns in diameter or smaller are indetectable. CONCLUSIONS: Although a direct sonographic--histologic correlation is impossible for small vessels, a systematic assessment of the size distribution in clearly identifiable regions permits to estimate the sensitivity of color Doppler to detect blood flow in small vessels. According to our results, capillary blood flow is indetectable, and precapillary vessels may be detected only under optimal conditions.