Uterine cervical carcinoma: comparison of standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as for therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this study to: (a) examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis [microvessel density (MVD) and vascular endothelial growth factor (VEGF)]; and (b) determine the ultimate value of a histomorphological and a dynamic MRI approach by the correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) and standard parameters [the maximum signal intensity increase over baseline (SI-I) and the steepest signal intensity-upslope per second (SI-U/s)] were calculated from a contrast-enhanced dynamic MRI series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD and VEGF) were compared to MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05 and 0.001, respectively) worse disease outcome than did tumors with low k21 and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD and VEGF) had any significant power to predict patient survival. It is concluded that in patients with uterine cervical cancer: (a) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF expression; (b) a functional, dynamic MRI approach (both standard and pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than are the current histomorphological-based markers of tumor angiogenesis; and (c) compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.

Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic involvement in uterine cervical cancer.

Angiogenic activity of cervical carcinoma: assessment by functional magnetic resonance imaging-based parameters and a histomorphological approach in correlation with disease outcome.

Angiogenesis plays a fundamental role in tumor growth and metastasis. What is needed is a quantitative, noninvasive, and repeatable assay to estimate functional angiogenic activity of the entire tumor. The aims of the present study were to: (a) examine the relationship between functional magnetic resonance imaging (MRI)-based parameters with established histomorphological markers of tumor angiogenesis [histological microvessel density (HMVD) and vascular endothelial growth factor expression (VEGF)]; and (b) determine the ultimate value of both approaches to assess functional angiogenic active hotspots as markers of disease outcome in patients with cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, tissue exchange rate constant k21) were calculated from contrast-enhanced dynamic MRI series in 57 patients (mean age, 49 +/- 14 years) with biopsy proven uterine cervical cancer. Both pharmacokinetic parameters were correlated to histomorphologically determined areas of high HMVD and VEGF expression obtained from the operative specimens after radical surgery. In addition, the functional MRI and histomorphological data were used to assess disease outcome. A significant association was found between HMVD and the amplitude A (P < 0.001) and a less pronounced association with k21, (P < 0.05), respectively. No significant associations were found between the pharmacokinetic parameters (A, k21) and VEGF expression. When stratified into high and low median k21 groups, median k21 values >5.4 min(-1) were the only significant (P < 0.05) factors in predicting poor patient survival. None of the histomorphological markers of angiogenesis (HMVD or VEGF expression) showed any predictive power. We have found that: (a) focal hotspots of HMVD are the pathophysiological basis for differences in functional MRI; (b) areas of high microvessel density and microvessel permeability do not necessarily coincide, as demonstrated by the histomorphological and functional MRI findings; (c) the functional angiogenic activity of a tumor may not be sufficiently characterized by a histomorphological approach but rather by a functional MRI-based approach; and (d) functional MRI-based analysis may assess tumor angiogenic activity in terms of disease outcome more comprehensively than the histomorphological approach.

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.

Contrast-enhanced magnetization transfer imaging: improvement of brain tumor conspicuity and delineation for radiosurgical target volume definition.

PURPOSE: To assess the contrast-noise-ratio (CNR), and thus tumor conspicuity and delineation, on contrast-enhanced T1-weighted magnetization transfer (MT) images compared to conventional T1-weighted spin echo (SE) images as a strategy to improve definition of the macroscopic boost volume in radiosurgery treatment planning in patients with high grade gliomas or metastatic brain lesions. MATERIALS AND METHODS: Fifty patients (mean age, 51 years) with histologically proven or suspected high grade glioma or cerebral metastases were prospectively examined by MR imaging. Following gadolinium dimeglumine administration (0.1 mmol/kg body weight) the brain was imaged with both a T1-weighted MT-fast low angle shot (FLASH) pulse sequence and with a conventional T1-weighted SE sequence without MT saturation. Lesion conspicuity, size and CNR were compared for both techniques. RESULTS: The mean tumor diameter of malignant gliomas was significantly (P < 0.01) larger when measured on T1-weighted MT-FLASH images compared to T1-weighted SE images and was comparable for metastatic lesions. The mean CNR of enhancing lesions on T1-weighted MT-FLASH was 14 +/- 5 compared to 10 +/- 4 on SE images, representing a significant (P < 0.05) improvement. Lesion conspicuity and delineation was improved in 10 of 20 patients (50%) with high grade gliomas and in 15 of 30 patients (50%) with metastases. Additional contrast enhancing lesions were detected in 8 of 30 patients (27%) with metastases on MT-FLASH images. Lesion conspicuity was markedly improved in the posterior fossa. DISCUSSION: Contrast-enhanced T1-weighted MT-FLASH images improve lesion detection and delineation in the planning process of radiosurgery in patients with intracranial high grade gliomas or metastases and may even alter the treatment approach.

Abdominal aortic aneurysm. Detection of multilevel vascular pathology by time-resolved multiphase 3D gadolinium MR angiography: initial report.

OBJECTIVE: To evaluate multiphasic 3D gadolinium-enhanced magnetic resonance angiography (3D-Gd-MRA) for detection of vascular pathology at multiple levels of the aorta and iliac arteries. METHODS: In 18 patients with abdominal aortic aneurysm (n = 13), dissection (n = 3), or both (n = 2), multiphase 3D-Gd-MRA was performed acquiring five consecutive (6.8 seconds) 3D data sets in a single breath-hold. In each of the five time-resolved phases, vessel visibility of the abdominal aortic branches and iliac arteries was assessed. The extent of vessel involvement by the aneurysm or dissection seen on multiphase 3D-Gd-MRA was compared with standard imaging and surgical findings. Digital subtraction angiography was available for comparison in 4 cases, CT angiography in 10 cases. RESULTS: Due to the delayed filling of the aortic aneurysm, the proximal aortic branches and the aneurysm neck demonstrated an inversely related enhancement compared with the distal abdominal and iliac vessels (P < 0.001). Review of all five phases of multiphase 3D-Gd-MRA allowed optimal visualization of each vessel segment without any artifacts due to parenchymal or venous overlay. In dissections, review of three phases was required (P < 0.001) for diagnostic evaluation of the true and false lumens. Substantially more vessel involvement was detected on multiphase 3D-Gd-MRA; this was surgically confirmed in 10 of 11 cases and affected therapy management in 11 of 18 cases. CONCLUSIONS: Multiphase 3D-Gd-MRA is a convenient, robust, and safe technique for presurgical anatomic mapping of complex aortic aneurysms and dissections.

Radiosurgical treatment planning of brain metastases based on a fast, three-dimensional MR imaging technique.

A fast, three-dimensional (3D) sequence for magnetic resonance (MR) imaging of the brain and its application in radiosurgical treatment planning of brain metastases is reported. The measuring sequence (MPRAGE) requires magnetization-prepared 180 degrees inversion pulses followed by rapid low angle excitation pulses and gradient-echoes for image generation. The resulting T1-weighted MPRAGE images were compared with two-dimensional (2D) T1-weighted spin-echo (SE) images after administration of 0.1 mmol/kg b.w. Gd-DTPA in 10 patients with known brain metastases. Original or multiplanar reformatted images obtained from a 128 partition data set of the 3D MPRAGE sequence offered comparable diagnostic quality to that of 2D SE imaging. Gd-DTPA enhancement and lesion targeting was similar in most of the patients in SE as well as MPRAGE imaging. During imaging and therapy the patient's head was fixed in a stereotactic localization system which is usable at the MR and the linear accelerator installations. The dose calculation of the radiosurgery planning was based on 3D MR imaging data assuming a homogenous attenuation value inside the head which was sufficient for an accurate dose calculation since tissue inhomogeneities do not significantly influence the shape of the relative dose distribution especially for radiosurgery of the brain. Under this circumstance the dose calculation can be based only on the 3D geometric conformation of the patient's head. A simple algorithm for treatment planning can be used if the MR data are free of geometric distortion.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracranial meningeomas: time- and dose-dependent effects of irradiation on tumor microcirculation monitored by dynamic MR imaging.

The purpose of this study was the characterization of the time- and dose-dependent effects of irradiation on tumor microcirculation by means of dynamic MR imaging and correlation of the estimated data with tumor response in patients with meningeomas. Dynamic MR imaging studies were performed in 20 patients with intracranial meningeomas prior to (n = 20) and at 6 (n = 17), 18 (n = 17), and 50 wk (n = 14) after the end of radiotherapy. In seven of these patients, dynamic measurements were also performed during fractionated radiotherapy after approximate 20 Gy and 54 Gy. During and after short-time infusion of gadopentetate dimeglumine, the kinetics of lesion response was resolved using a strongly T1-weighted saturation recovery TurboFLASH (SRTF) sequence. The signal-time courses of the suspected lesions were analyzed using a pharmacokinetic two-compartment model. The calculated parameters amplitude A (reflecting gadopentetate dimeglumine accumulation in the extracellular space) and exchange rate constant k21 (depending on vascular permeability and blood flow) were displayed as color-coded images and analyzed as a function of time of therapy and radiation dose. All meningeomas showed a high exchange rate constant k21 (median, 5.7 min-1; range, 1.9-23.0 min-1) and a high amplitude A (median, 1.5 arbitrary units; range, 1.1-2.7) prior to X-ray treatment. During radiotherapy we found a dose related significant (p < .01) increase of k21 accompanied by an increase of the amplitude A as compared to the pretreatment values. Analysis of tumor volume 6, 18, and 50 wk after X-ray treatment revealed two different groups. In the responder group (n = 13) the median of the tumor volume decreased from 10.0 to 7.5 cm3. For this group, we found a significant drop (p < .01) of the median of the amplitude A and a decrease of the exchange rate constant k21. In the nonresponder group (n = 4) the median of the tumor volume increased after radiation from 3.5 to 4.5 cm3. The pharmacokinetic analysis revealed a decrease of the amplitude A-and an increase of the exchange rate constant k21. The response of meningeomas to radiotherapy is influenced by the effect of X-rays on tumor microcirculation. This effect on tumor microcirculation can be derived by analysis of pharmacokinetic maps obtained from dynamic MR images. Furthermore, these pharmacokinetic maps can possibly be used to differentiate groups of patients who respond or do not respond to radiotherapy and, thus, could benefit from another treatment modality.

Serial MR imaging of intracranial metastases after radiosurgery.

PURPOSE: To evaluate the spatiotemporal evolution of radiosurgical induced changes both in metastases and in normal brain tissue adjacent to the lesions by serial magnetic resonance (MR) imaging. METHODS AND MATERIALS: Thirty-five intracranial metastases of different primaries were treated in 25 patients by single high-dose radiosurgery. MR images acquired before radiosurgery were available in all patients. Sixty-three follow-up MR studies were performed in these patients including T2- and contrast-enhanced T1-weighted MR images. The average follow-up time was 9 +/- 5 months (mean +/- standard deviation [SD]). Based on contrast-enhanced T1-weighted MR images, tumor response was radiologically classified in the following four groups: stable disease was assumed if the average tumor diameter after treatment did not show a tumor shrinkage of more than 50% and an increase of more than 25%, partial remission as a shrinkage of tumor size of more than 50%, a disappearance of contrast-enhancing tumor as a complete remission, and an increase of tumor diameter of more than 25% as tumor progress. Moreover, we analysed signal changes on T2-weighted images in brain parenchyma adjacent to the enhancing metastases. RESULTS: The overall mean survival time was 10.5 +/- 7 months, with a 1-year actuarial survival rate of 40%. Stable disease, partial or complete remission of the metastatic tumor was observed in 22 patients (88%). Central or homogeneous loss of contrast enhancement appeared to be a good prognostic sign for stable disease or partial remission. This association was statistically significant (p < 0.05). Three patients (12%) suffered from tumor progression. In eight patients (32%) with stable disease or partial remission, signal changes on T2-weighted images were observed in tissue adjacent to the contrast enhancing lesions. A progression of the high signal on T2-weighted images was seen in seven of the eight patients between 3 and 6 months after therapy, followed by a signal regression 6-18 months after irradiation. CONCLUSION: MR imaging is a sensitive imaging tool to evaluate tumor response as well as the presence or absence of adjacent parenchymal changes following radiosurgery. Loss of homogeneous or central contrast enhancement on Gd-enhanced MR images appeared to be a good prognostic sign for tumor response. Tumor shrinkage seems not to be dependent on time. In addition, most cases of radiation induced changes in normal brain parenchyma observed on T2-weighted images seem to be self limited.

3D MPRAGE evaluation of lesions in the posterior cranial fossa.

Standard spin-echo images of the posterior cranial fossa are usually impaired by pulsation artifacts. We evaluated a heavily T1 weighted MPRAGE sequence (TR/TE/alpha/TI = 10/4/10-15 degrees/200-350) for detection of intracerebral lesions in the posterior fossa in 11 patients. Overall quality of the MPRAGE images was superior due to the lack of pulsation artifacts, high S/N and excellent gray-white matter contrast. Lesion detection was better in one patient, equal in six and inferior in four patients compared to SE technique. A cerebellar metastasis (8 mm) in one patient was completely blurred from pulsation artifacts on the SE images. Whereas multiple small lesions (< or = 4 mm) with discrete contrast enhancement were missed on the MPRAGE images in three patients. We conclude, that the MPRAGE sequence yields high quality images with isotropic spatial resolution in a reasonable time. But MPRAGE with these parameters can not replace standard SE images in screening the posterior fossa, because of a decreased sensitivity in the detection of small contrast-enhancing lesions.

Cerebral arteriovenous malformations: improved nidus demarcation by means of dynamic tagging MR-angiography.

Our purpose was to further improve the target volume definition for radiosurgical treatment of cerebral arteriovenous malformations (AVMs) by means of dynamic MRA (dMRA) using a blood bolus tagging sequence. We therefore compare this technique with 3D-TOF-MRA and transfemoral high resolution angiography in plain film technique. Twenty patients with angiographically proven cerebral AVMs were investigated by dMRA, TOF-MRA, and conventional angiography during the MR-assisted radiosurgical planning protocol. The patient's head was fixed in an MR-compatible stereotactic device. The different angiography techniques were evaluated by consensus of two radiologists. AVMs were characterized by the number and origin of feeding arteries, the maximum diameter of the AVM nidus, and the venous drainage pattern. Dynamic MRA was able to demonstrate the complete AVM characteristics and hemodynamics in 12 out of 20 patients. In three patients with an AVM nidus smaller than 1 cm in diameter the technique could not reliably depict the malformation. Technical problems due to steel screws and pins in the initially used stereotactic frame occurred in five patients. Due to reduced vessel overlap and the lack of disturbances caused by formations with short T1 time, dMRA was superior to TOF-MRA in the detection and the exact localization of the AVM nidus in four patients. We conclude that dMRA is able to demonstrate reliably AVM characteristics and hemodynamics in AVMs with a nidus larger than 1 cm in diameter. Because of the improved demarcation of the AVM nidus, this technique may be a valuable adjunct to radiosurgery planning of cerebral AVMs.

Macroscopic tumor volume of malignant glioma determined by contrast-enhanced magnetic resonance imaging with and without magnetization transfer contrast.

The purposes of this study were to compare the conspicuity and lesion volume of contrast-enhancing macroscopic malignant glioma determined by postcontrast magnetic resonance (MR) imaging with and without magnetization transfer (MT) saturation, and to discuss possible implications for radiotherapy planning. Nineteen patients (age 24-60 years) with histologically proven malignant glioma were prospectively examined by MR imaging. After the administration of gadolinium dimeglumine (0.1 mmol/kg body weight), the lesions were imaged with an MT-weighted FLASH (fast, low-angle shot) pulse sequence and with a conventional T1-weighted spin-echo (SE) sequence without MT saturation. The mean tumor volumes of gliomas measured on MT-weighted FLASH images were significantly (p < .01) larger than those obtained from T1-weighted SE images (45 +/- 15 cm3 vs. 33 +/- 10 cm3). The mean contrast-to-noise ratio of enhancing lesions on MT-weighted FLASH was 48 +/- 14 compared with 30 +/- 14 on SE images, representing a significant (p < .01) improvement. We conclude that the volume of contrast enhancement of malignant glioma identified on MT-weighted FLASH images represents the area of disrupted blood-brain barrier. If this volume of subtle contrast enhancement is caused by tumor infiltration and represents the boost target volume for stereotactic radiosurgery or brachytherapy, MT-weighted FLASH images would be better than T1-weighted SE images to define these volumes. These improved delineation of areas at highest risk for recurrence following radiation therapy should enhance the efficacy of treatment planning for high-boost therapy.

Magnetically labeled water perfusion imaging of the uterine arteries and of normal and malignant cervical tissue: initial experiences.

PURPOSE: The aim of this pilot study was to evaluate a magnetically labeled water perfusion imaging technique as a non-contrast-enhanced approach to demonstrate the uterine artery, its branches, and to assess the cervical uterine blood flow in healthy volunteers and in patients with advanced uterine cervical carcinoma (FIGO IIB-IVA). METHODS AND MATERIALS: Seven healthy volunteers (mean age, 29 years) and twenty-two patients (mean age, 52 years) with advanced cancer of the uterine cervix (FIGO IIB-IVA) were prospectively examined by magnetically labeled water perfusion imaging at different inversion delay times (300-900 ms). The magnetic resonance imaging (MRI) findings of all patients were matched to the findings of contrast-enhanced dynamic MRI and multiple biopsies (n = 5) and/or surgical whole mount specimens (n = 17), which were available in all patients. RESULTS: The uterine artery was well visualized with short inversion delay times of 300-500 ms. It was characterized as single or multiple helical loops before dividing into its intracervical branches. The intracervical branching was observed at inversion delay times of 500-700 ms. With longer inversion delay times, arterial signal enhancement disappeared and cervical tissue enhancement was noted. Enhancement of benign tissue was observed at inversion delay times of 1100-1700 ms and in malignant tissue at shorter inversion delay times of 900-1300 ms. The maximum of this diffuse signal enhancement of benign tissue was seen at inversion delay times of 1500 ms (1100-1700 ms) in malignant tissue at significantly (p < 0.5) shorter inversion delay times of 1100 ms (900-1300 ms). CONCLUSION: Our preliminary results show that the vascular supply and blood flow of the normal uterine cervix and of advanced cervical cancer can be assessed by magnetically labeled water perfusion imaging and that malignant cervical tissue is earlier and stronger perfused than normal cervical tissue.

[MR tomographic monitoring of prostate carcinoma after cryotherapy: initial results]. / MR-tomographische Verlaufskontrollen des Prostatakarzinoms nach Cryotherapie: Erste Ergebnisse.

PURPOSE: To assess the morphological changes in the prostate gland and adjacent tissue after cryosurgery by high resolution MRI in patients with histological proven prostatic carcinoma. METHOD: 15 patients (mean age 66 years) with histologically proven prostate carcinoma underwent T2- and contrast-enhanced T1-weighted high-resolution MRI examinations with fat suppression. Follow-up MRI with an identical imaging protocol were performed at different time intervals (24-72 h, 2-6, 12, 26-52 weeks). RESULTS: Mean prostate volume had decreased by 30% in all patients 12-52 weeks after cryosurgery. After cryosurgery, zonal differentiation was lost in all patients with abnormalities in the periprostatic tissue in all patients, and rectal wall thickening in 47% of patients. Cryosurgery-induced changes in the prostate could not be differentiated from tumour recurrence. CONCLUSION: High resolution MRI allows precise recognition of intraprostatic and adjacent tissue alterations after cryosurgery of prostatic carcinoma. However, reliable detection of tumour recurrence was impossible due to cryosurgically induced signal changes.

[Detection of angiogenesis-dependent parameters by functional MRI: correlation with histomorphology and evaluation of clinical relevance as prognostic factor using cervix carcinoma as an example]. / Erfassung angiogeneseabhängiger Parameter mittels funktioneller MRT: Korrelation mit der Histomorphologie sowie Abklärung der klinischen Relevanz als Prognosefaktor am Beispiel des Zervixkarzinomes.

PURPOSE: Purpose of this study is to compare functional MRI parameters with histomorphological markers of tumor microvessel density (MVD) and permeability (vascular endothelial growth factor) and to determine the ultimate value of both approaches by correlation with disease outcome in patients with primary cancer of the uterine cervix. METHOD: Pharmacokinetic parameters were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the operative whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using logrank statistics. RESULTS: Significant (p < 0.05-0.01) associations were found between MVD and dynamic MRI parameters. No significant relationships were observed between VEGF expression and dynamic MRI parameters. Disease outcome was better assessed with dynamic MRI parameters than with the histomorphological approach. CONCLUSIONS: It is concluded that 1) the pathophysiological basis for the amplitude A in dynamic MRI is MVD but not VEGF expression; and 2) a functional, dynamic MRI approach may be more suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis.

[Angiogenesis in cervical cancer]. / L'angiogenèse dans le cancer du col utérin.

Angiogenesis is a factor of spread and metastatization. This fact has been established for many malignancies, but the data concerning cervical cancer are rather conflicting. In a study including 42 patients affected by cervical cancer stages IB to IVA, the authors assess the mean capillary density and the correlations between this parameter and the other anatomoclinical parameters: the VEGF expression, tumoral oxygenation and the data obtained from dynamic MRI. The histologic assessment of the capillary density and the data obtained by dynamic MRI enable us at the same time to quantify the tumoral angiogenesis and establish the prognosis. The two methods could be used routinely as markers of prognosis. VGEF surely plays a role in angiogenesis linked with cervical cancer growth, but its regulation is not definitively clear at the moment. The impact of tumoral oxygenation (whose place as a prognostic marker is clearly established) on tumoral angiogenesis and vessels' permeability as well as its control is currently not clearly established. Further studies on larger populations are necessary.

Cure in a patient with multiple osseus metastases in non-small cell lung cancer: a case report.

PURPOSE: This case was reported to describe a case of cure in a 61-year old patient with squamous cell lung cancer and multiple extrathoracic metastasis. METHODS AND MATERIALS: A left upper lobectomy of lung for a squamous cell carcinoma was performed on a 61-year old man with curative intent. Four months later two osseus metastases were irradiated with Cobalt 60 up to 40 Gy. RESULTS: The two irradiated lesions showed continuously shrinkage as well as signs of recalcification. Eleven years later the patient shows clinically absolute well being and on CT there are no signs of recurrent disease of the lung or bone anymore. DISCUSSION: To our knowledge has nobody so far reported of a case of as squamous cell lung cancer which was operated and irradiated on thus resulting in cure. Further on the authors discuss that it might well be worthwhile to define subgroups in stage 4 non-small cell lung cancer (presence of extrathoracic metastases) which might benefit from a more aggressive treatment approach than pure palliation.

[Progress in understanding spinal cord injuries. Clinical aspects, imaging, pathological correlations]. / Fortschritte im Verständnis der Rückenmarkverletzungen. Klinik, Bildgebung, pathologische Korrelationen.

Close inspection of MR images in all stages of SCI can reveal alterations which are important for our understanding of the changes which occur in SCI and may be crucial for planning surgical intervention. Importantly also, these observations may assist in the evaluation of novel therapies in SCI, such as cellular transplantation. It is hopeful that MR strategies which are currently in routine use in the brain, such as diffusion weighted imaging, perfusion studies, spectroscopy, and magnetization transfer can be adopted for use in the spine [8]. Because of the small size of the cord, the magnetic susceptibility problems caused by surrounding air and bone, and nearby vascular and CSF flow/pulsations, these techniques are currently very difficult to employ in the cord. They will however evolve over time and give us greater insights into the in-vivo status of the injured cord.

[Diffusion weighted MRI: ischemic and traumatic injuries of the central nervous system]. / Diffusionsgewichtete MRI: Ischämische und traumatische Verletzungen des Zentralnervensystems.

Diffusion weighted magnetic resonance imaging (DWI) represents a recent development that extends imaging from the depiction of the neuroanatomy into the field of functional and physiologic processes. DWI measures a fundamentally different physiologic parameter than conventional MRI. Image contrast is related to differences in the microscopic motion (diffusion) of water molecules within brain tissue rather than a change in total tissue water. Consequently, DWI can reveal pathology where conventional T1- and T2-weighted MR images are negative. DWI has clinically proven its value in the assessment of acute cerebral stroke and trauma by showing cerebral injury early due to ist ability to discriminate between lesions with cytotoxic edema (decreased diffusion) from lesions with vasogenic edema (increased diffusion). Full tensor DWI allows to calculate a variety of functional maps, the most widely used maps include maps of apparent diffusion coefficients and isotropic diffusion. In addition maps of anisotropic diffusion can be calculated which are believed to give information about the integrity and location of fiber tracts. This functional-anatomical information will most probably play an increasingly important role in the early detection of primary and secondary tissue injury from various reasons and could guide and validate current and future neuroprotective treatments.