Multiphase contrast-enhanced CT with highly concentrated contrast agent can be used for PET attenuation correction in integrated PET/CT imaging.

PURPOSE: State-of-the-art positron emission tomography/computed tomography (PET/CT) systems incorporate multislice CT technology, thus facilitating the acquisition of multiphase, contrast-enhanced CT data as part of integrated PET/CT imaging protocols. We assess the influence of a highly concentrated iodinated contrast medium (CM) on quantification and image quality following CT-based attenuation correction (CT-AC) in PET/CT. METHODS: Twenty-eight patients with suspected malignant liver lesions were enrolled prospectively. PET/CT was performed 60 min after injection of 400 MBq of (18)F-fluorodeoxyglucose (FDG) and following the biphasic administration of an intravenous CM (400 mg iodine/ml, Iomeron 400). PET images were reconstructed with CT-AC using any of four acquired CT image sets: non-enhanced, pre-contrast (n-PET), arterial phase (art-PET), portal venous phase (pv-PET) and late phase (late-PET). Normal tissue activity and liver lesions were assessed visually and quantitatively on each PET/CT image set. RESULTS: Visual assessment of PET following CT-AC revealed no noticeable difference in image appearance or quality when using any of the four CT data sets for CT-AC. A total of 44 PET-positive liver lesions was identified in 21 of 28 patients. There were no false-negative or false-positive lesions on PET. Mean standardized uptake values (SUV) in 36 evaluable lesions were: 5.5 (n-PET), 5.8 (art-PET), 5.8 (pv-PET) and 5.8 (late-PET), with the highest mean increase in mean SUV of 6%. Mean SUV changes in liver background increased by up to 10% from n-PET to pv-PET. CONCLUSION: Multiphase CT data acquired with the use of highly concentrated CM can be used for qualitative assessment of liver lesions in torso FDG PET/CT. The influence on quantification of FDG uptake is small and negligible for most clinical applications.

Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis.

Pulmonary fibrosis is the consequence of a variety of diseases with no satisfying treatment option. Therapy-induced fibrosis also limits the efficacy of chemotherapy and radiotherapy in numerous cancers. Here, we studied the potential of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors (RTKIs) to attenuate radiation-induced pulmonary fibrosis. Thoraces of C57BL/6 mice were irradiated (20 Gy), and mice were treated with three distinct PDGF RTKIs (SU9518, SU11657, or Imatinib). Irradiation was found to induce severe lung fibrosis resulting in dramatically reduced mouse survival. Treatment with PDGF RTKIs markedly attenuated the development of pulmonary fibrosis in excellent correlation with clinical, histological, and computed tomography results. Importantly, RTKIs also prolonged the life span of irradiated mice. We found that radiation up-regulated expression of PDGF (A-D) isoforms leading to phosphorylation of PDGF receptor, which was strongly inhibited by RTKIs. Our findings suggest a pivotal role of PDGF signaling in the pathogenesis of pulmonary fibrosis and indicate that inhibition of fibrogenesis, rather than inflammation, is critical to antifibrotic treatment. This study points the way to a potential new approach for treating idiopathic or therapy-related forms of lung fibrosis.

Respiratory-induced prostate motion: characterization and quantification in dynamic MRI.

BACKGROUND AND PURPOSE: To investigate prostate movement during deep breathing and contraction of abdominal musculature by means of dynamic MRI and analyze implications for image-guided radiotherapy of prostate cancer. PATIENTS AND METHODS: A total of 43 patients and 8 healthy volunteers were examined with MRI. Images during deep respiration and during contraction of abdominal musculature (via a coughing maneuver) were obtained with dynamic two-dimensional (2D) balanced SSFP; 3 frames/s were obtained over an acquisition time of 15 s. Images were acquired in sagittal orientation to evaluate motion along both the craniocaudal (cc)-axis and anteroposterior (ap)-axis. Prostate motion was quantified semi-automatically using dedicated software tools. RESULTS: Respiratory induced mean cc-axis displacement of the prostate was 2.7 ± 1.9 (SD) mm (range, 0.5-10.6 mm) and mean ap-axis displacement 1.8 ± 1.0 (SD) mm (range, 0.3-10 mm). In 69% of the subjects, breathing-related prostate movements were found to be negligible (< 3 mm). The prostate displacement for abdominal contraction was significantly higher: mean cc-axis displacement was max. 8.4 ± 6.7 (SD) mm (range, 0.6-27 mm); mean anteroposterior movement was 8.3 ± 7.7 (SD) mm (range, 0.7-26 mm). CONCLUSION: Dynamic MRI is an excellent tool for noninvasive real-time imaging of prostate movement. Further investigations regarding possible applications in image-guided radiotherapy, e.g., for individualized planning and in integrated linac/MRI systems, are warranted.

Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro.

BACKGROUND: Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. MATERIAL AND METHODS: HIF-1α expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1α siRNA sequence primers. Quantitative real-time polymerase chain reaction assay was performed to quantify the mRNA expression of HIF-1α. HIF-1α protein levels were studied by Western blotting at 20% (air) or after 12 hours at 0.1% O2 (hypoxia). Cells were assayed for clonogenic survival after irradiation with 2, 5, or 10 Gy, under normoxic or hypoxic conditions in the presence of HIF-1α-targeted or control siRNA sequences. A modified oxygen enhancement ratio (OER´) was calculated as the ratio of the doses to achieve the same survival at 0.1% O(2) as at ambient oxygen tensions. OER´ was obtained at cell survival levels of 50%, 37%, and 10%. RESULTS: HIF-1α-targeted siRNA enhanced radiation treatment efficacy under severely hypoxic conditions compared to tumor cells treated with scrambled control siRNA. OER was reduced on all survival levels after treatment with HIF-1α-targeted siRNA, suggesting that inhibition of HIF-1 activation by using HIF-1α-targeted siRNA increases radiosensitivity of hypoxic tumor cells in vitro. CONCLUSION: Inhibition of HIF-1 activation by using HIF-1α-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro.

Tumor cell metabolism imaging.

Molecular imaging of tumor metabolism has gained considerable interest, since preclinical studies have indicated a close relationship between the activation of various oncogenes and alterations of cellular metabolism. Furthermore, several clinical trials have shown that metabolic imaging can significantly impact patient management by improving tumor staging, restaging, radiation treatment planning, and monitoring of tumor response to therapy. In this review, we summarize recent data on the molecular mechanisms underlying the increased metabolic activity of cancer cells and discuss imaging techniques for studies of tumor glucose, lipid, and amino acid metabolism.

Positron emission tomography/computed tomography and whole-body magnetic resonance imaging in staging of advanced nonsmall cell lung cancer--initial results.

OBJECTIVE: To evaluate and compare positron emission tomography/computed tomography (PET/CT) with whole-body magnetic resonance imaging (wbMRI) in the correct staging of patients with advanced nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Fifty-two patients with an NSCLC stage IIIa or IIIb (36 males and 16 females) were included in this study. Patients were referred to our department for restaging. Within 1 week PET/CT and wbMRI were performed in all patients. Images were examined independently by 2 experienced physicians from the Department of Nuclear Medicine and Radiology. Afterward, consensus reading was performed. In 22 patients, surgery served as gold standard, whereas in 30 patients, follow-up controls (after 2 months) were performed. RESULTS: The use of wbMRI correctly T-staged all patients. Especially volume interpolated breathhold examination sequence correctly T-staged all tumors. PET/CT did not correctly stage chest wall infiltration in 4 cases [sensitivity 92.3% (P < 0.05 to wbMRI)/specificity 100%], verified by surgery. PET/CT correctly N-staged 51 patients (sensitivity 96.1%/specificity 100%). WbMRI showed a significant tendency to understage N-status [sensitivity 88.5% (P < 0.05)/specificity 96.1%]. Different N-status by PET/CT changed operability in 4 patients. In 2 patients, distant metastases were detected by both techniques. CONCLUSION: In the correct staging of advanced NSCLC, PET/CT has advantages in N-staging. This is of high relevance for therapy planning. WbMRI especially using volume interpolated breathhold examination sequences, has certain advantages in T-staging.

Prospective comparison of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and whole-body magnetic resonance imaging in staging of advanced malignant melanoma.

The aim of our study was to compare the overall and site-based accuracy and impact on patient management of positron emission tomography/computed tomography (PET/CT) and whole-body (wb) magnetic resonance imaging (MRI) in staging of advanced melanoma. In a prospective blinded study, 64 patients with American Joint Committee on Cancer (AJCC) stage III/IV melanoma underwent 18F-fluorodeoxyglucose PET/CT and wbMRI. In total 420 lesions were evaluated. The overall accuracy of PET/CT was 86.7% compared to 78.8% for wbMRI (P=0.0007). PET/CT was significantly more accurate in N-staging and detecting of skin and subcutaneous metastases, whereas wbMRI was more sensitive in detecting liver, bone and brain metastases. WbMRI was less sensitive but more specific than PET/CT in classifying pulmonary lesions. In 41 patients (64%) whole-body imaging caused changes of treatment. Whole-body staging of patients with advanced melanoma is most accurate by combining wbPET/CT and organ-specific wbMRI including a brain, liver and bone marrow protocol.

Assessment of morphological MRI for pulmonary changes in cystic fibrosis (CF) patients: comparison to thin-section CT and chest x-ray.

OBJECTIVES: As pulmonary complications are life limiting in patients with cystic fibrosis (CF), repeated chest imaging [chest x-ray, computed tomography (CT)] is needed for follow up. With the continuously rising life expectancy of CF patients, magnetic resonance imaging (MRI) as a radiation-free imaging modality might become more and more attractive. The goal of this study was to prospectively assess the value of MRI for evaluation of morphologic pulmonary CF-changes in comparison to established imaging modalities. MATERIALS AND METHODS: Thirty-one CF patients (19 female, 12 male; mean age 16.7 years) with stable lung disease were examined by MRI: HASTE, coronal/transversal (TR/TE/alpha/TA: infinite/28 ms/180 degrees /18 s), multi-detector computed tomography (MDCT) (30 patients): 120 kV, dose modulated mAs, and chest x-ray (21 patients). Image evaluation: random order, 4 chest radiologists in consensus; chest x-ray: modified Chrispin-Norman score; CT and MRI: modified Helbich score. The maximal attainable score for chest x-ray was 34, for MRI and CT 25. Median scores, Pearson correlation coefficients, Bland-Altman plots, and concordance of MRI to CT on a lobar and segmental basis were calculated. RESULTS: The median MRI and MDCT scores were 13 (min 3, max 20) respectively 13.5 (min 0, max 20). The median chest x-ray score was 14 (min 5, max 32). Pearson correlation coefficients: MRI/CT = 0.80, P < 0.0001; MRI/chest x-ray = 0.63, P < 0.0018; chest x-ray/CT = 0.75, P < 0.0001. The median lobe related concordance was 80% for bronchiectasis, 77% for mucus plugging, 93%, for sacculation/abscesses, and 100% for collapse/consolidation. CONCLUSIONS: Morphologic MRI of the lung in CF patients demonstrates comparable results to MDCT and chest x-ray. Because radiation exposure is an issue in CF patients, MRI might have the ability to be used as an appropriate alternative method for pulmonary imaging.

Tumor detection by diffusion-weighted MRI and ADC-mapping--initial clinical experiences in comparison to PET-CT.

OBJECTIVE: To evaluate the clinical potential of diffusion-weighted-imaging (DWI) with apparent diffusion coefficient (ADC)-mapping for tumor detection. MATERIALS AND METHODS: A single-shot echo-planar-imaging DWI sequence with fat suppression and ability for navigator-based respiratory triggering was implemented. Nineteen patients (11 melanoma, 4 prostate cancer, 1 non-Hodgkin lymphoma, and 3 lung cancer) were examined by positron emission tomography (PET) with an integrated computed tomography scanner (PET-CT) and DWI. Images at b = 0, 400, and 1000 s/mm2 were acquired and ADC maps were generated. PET examinations were used as a reference for tumor detection. Four hundred twenty-four regions of interest were used for DWI and 73 for PET data evaluation. RESULTS: DWI and ADC maps were of diagnostic quality. Metastases with increased tracer uptake were clearly visualized at b = 1000 s/mm2 with the exception of mediastinal lymph node metastases in cases of lung cancer. ADC mapping did not improve detection rates. CONCLUSIONS: DWI is a feasible clinical technique, improving the assessment of metastatic spread in routine magnetic resonance imaging examinations.

Monitoring of lung motion in patients with malignant pleural mesothelioma using two-dimensional and three-dimensional dynamic magnetic resonance imaging: comparison with spirometry.

PURPOSE: To monitor lung motion in patients with malignant pleural mesothelioma (MPM) before and after chemotherapy (CHT) using 2-dimensional (2D) and 3-dimensional (3D) dynamic MRI (dMRI) in comparison with spirometry. METHODS AND MATERIALS: Twenty-two patients with MPM were examined before CHT, as well as after 3 and 6 CHT cycles (3 months and 6 months) using 2D dMRI (trueFISP; 3 images/s) and 3D dMRI (FLASH 3D, 1 slab (52 slices)/s) using parallel imaging in combination with view-sharing technique. Maximum craniocaudal lung dimensions (2D) and lung volumes (3D) were monitored, separated into the tumor-bearing and nontumor-bearing hemithorax. Vital capacity (VC) was measured for comparison using spirometry. RESULTS: Using 2D technique, there was a significant difference between the tumor-bearing and the nontumor-bearing hemithorax before CHT (P < 0.01) and after 3 CHT cycles (P < 0.05), whereas difference was not significant in the second control. In the tumor-bearing hemithorax, mobility increased significantly from the status before versus after 3 CHT cycles (4.1 +/- 1.1 cm vs. 4.8 +/- 1.4 cm, P < 0.05). Using 3D technique, at maximum inspiration, the volume of the tumor-bearing hemithorax was 0.6 +/- 0.4 L and of the nontumor-bearing hemithorax 1.25 +/- 0.4 L before CHT. In the follow-up exams, these volumes changed to 1.05 +/- 0.4 L (P < 0.05) and 1.4 +/- 0.5 L, respectively. Using spirometry, there was no significant change in VC (1.9 +/- 0.4 L vs. 2.2 +/- 0.7 L vs. 2.2 +/- 0.9 L). CONCLUSION: dMRI is capable of monitoring changes in lung motion and volumetry in patients with MPM not detected by global spirometry. Thus, dMRI is proposed for use as a further measure of therapy response.

Small molecule receptor tyrosine kinase inhibitor of platelet-derived growth factor signaling (SU9518) modifies radiation response in fibroblasts and endothelial cells.

BACKGROUND: Several small receptor tyrosine kinase inhibitors (RTKI) have entered clinical cancer trials alone and in combination with radiotherapy or chemotherapy. The inhibitory spectrum of these compounds is often not restricted to a single target. For example Imatinib/Gleevec (primarily a bcr/abl kinase inhibitor) or SU11248 (mainly a VEGFR inhibitor) are also potent inhibitors of PDGFR and other kinases. We showed previously that PDGF signaling inhibition attenuates radiation-induced lung fibrosis in a mouse model. Here we investigate effects of SU9518, a PDGFR inhibitor combined with ionizing radiation in human primary fibroblasts and endothelial cells in vitro, with a view on utilizing RTKI for antifibrotic therapy. METHODS: Protein levels of PDGFR-alpha/-beta and phosphorylated PDGFR in fibroblasts were analyzed using western and immunocytochemistry assays. Functional proliferation and clonogenic assays were performed (i) to assess PDGFR-mediated survival and proliferation in fibroblasts and endothelial cells after SU9518 (small molecule inhibitor of PDGF receptor tyrosine kinase); (ii) to test the potency und selectivity of the PDGF RTK inhibitor after stimulation with PDGF isoforms (-AB, -AA, -BB) and VEGF+bFGF. In order to simulate in vivo conditions and to understand the role of radiation-induced paracrine PDGF secretion, co-culture models consisting of fibroblasts and endothelial cells were employed. RESULTS: In fibroblasts, radiation markedly activated PDGF signaling as detected by enhanced PDGFR phosphorylation which was potently inhibited by SU9518. In fibroblast clonogenic assay, SU9518 reduced PDGF stimulated fibroblast survival by 57%. Likewise, SU9518 potently inhibited fibroblast and endothelial cell proliferation. In the co-culture model, radiation of endothelial cells and fibroblast cells substantially stimulated proliferation of non irradiated fibroblasts and vice versa. Importantly, the RTK inhibitor significantly inhibited this paracrine radiation-induced fibroblast and endothelial cell activation. CONCLUSION: Radiation-induced autocrine and paracrine PDGF signaling plays an important role in fibroblast and endothelial cell proliferation. SU9518, a PDGFR tyrosine kinase inhibitor, reduces radiation-induced fibroblast and endothelial cell activation. This may explain therapeutic anticancer effects of Imatinib/Gleevec, and at the same time it could open a way of attenuating radiation-induced fibrosis.

MRI Measurement of the hemodynamics of the pulmonary and systemic arterial circulation: influence of breathing maneuvers.

OBJECTIVE: The purpose of this study was to use phase-contrast MRI to evaluate the influence of various breathing maneuvers on the hemodynamics of the pulmonary and systemic arterial circulation. SUBJECTS AND METHODS: Twenty-five volunteers were examined with phase-contrast MRI. Flow measurements were acquired in the aorta, pulmonary trunk, and left and right pulmonary arteries during deep, large-volume inspiratory breath-hold, expiratory breath-hold, and smooth respiration (no breath-hold). Parameters assessed were peak velocity, blood flow, velocity gradient, and acceleration time. RESULTS: Pulmonary blood flow and peak velocity were significantly reduced during inspiratory breath-hold and expiratory breath-hold compared with no breath-hold (p < 0.01). Pulmonary velocity gradient in inspiratory breath-hold was significantly (p

Influence of different breathing maneuvers on internal and external organ motion: use of fiducial markers in dynamic MRI.

PURPOSE: To investigate, with dynamic magnetic resonance imaging (dMRI) and a fiducial marker, the influence of different breathing maneuvers on internal organ and external chest wall motion. METHODS AND MATERIALS: Lung and chest wall motion of 16 healthy subjects (13 male, 3 female) were examined with real-time trueFISP (true fast imaging with steady-state precession) dMRI and a small inductively coupled marker coil on either the abdomen or thorax. Three different breathing maneuvers were performed (predominantly "abdominal breathing," "thoracic breathing," and unspecific "normal breathing"). The craniocaudal (CC), anteroposterior (AP), and mediolateral (ML) lung distances were correlated (linear regression coefficient) with marker coil position during forced and quiet breathing. RESULTS: Differences of the CC distance between maximum forced inspiration and expiration were significant between abdominal and thoracic breathing (p < 0.05). The correlation between CC distance and coil position was best for forced abdominal breathing and a marker coil in the abdominal position (r = 0.89 +/- 0.04); for AP and ML distance, forced thoracic breathing and a coil in the thoracic position was best (r = 0.84 +/- 0.03 and 0.82 +/- 0.03, respectively). In quiet breathing, a lower correlation was found. CONCLUSION: A fiducial marker coil external to the thorax in combination with dMRI is a new technique to yield quantitative information on the correlation of internal organ and external chest wall motion. Correlations are highly dependent on the breathing maneuver.

Evaluation of lung volumetry using dynamic three-dimensional magnetic resonance imaging.

RATIONALE AND OBJECTIVES: We sought to investigate lung volume and surface measurements during the breathing cycle using dynamic three-dimensional magnetic resonance imaging (3D MRI). MATERIALS AND METHODS: Breathing cycles of 20 healthy volunteers were examined using a 2D trueFISP sequence (3 images/second) in combination with a model and segmented 3D FLASH sequence (1 image/second) MR images using view sharing. Segmentation was performed semiautomatically using an interactive region growing technique. Vital capacity (VC) was calculated from MRI using the model (2D) and counting the voxels (3D) and was compared with spirometry. RESULTS: VC from spirometry was 4.9+/-0.9 L, 4.4+/-1.2 L from 2D MRI measurement, and 4.7+/-0.9 L for 3D MRI. Using the 3D technique, correlation to spirometry was higher than using the 2D technique (r>0.95 vs. r>0.83). Using the 3D technique, split lung volumes and lung surface could be calculated. There was a significant difference between the left and right lung volume in expiration (P<0.05). CONCLUSIONS: Dynamic 3D MRI is a noninvasive tool to evaluate split lung volumes and lung surfaces during the breathing cycle with a high correlation to spirometry.

Effect of inspiratory and expiratory breathhold on pulmonary perfusion: assessment by pulmonary perfusion magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The effect of breathholding on pulmonary perfusion remains largely unknown. The aim of this study was to assess the effect of inspiratory and expiratory breathhold on pulmonary perfusion using quantitative pulmonary perfusion magnetic resonance imaging (MRI). METHODS AND RESULTS: Nine healthy volunteers (median age, 28 years; range, 20-45 years) were examined with contrast-enhanced time-resolved 3-dimensional pulmonary perfusion MRI (FLASH 3D, TR/TE: 1.9/0.8 ms; flip angle: 40 degrees; GRAPPA) during end-inspiratory and expiratory breathholds. The perfusion parameters pulmonary blood flow (PBF), pulmonary blood volume (PBV), and mean transit time (MTT) were calculated using the indicator dilution theory. As a reference method, end-inspiratory and expiratory phase-contrast (PC) MRI of the pulmonary arterial blood flow (PABF) was performed. RESULTS: There was a statistically significant increase of the PBF (delta = 182 mL/100 mL/min), PBV (delta = 12 mL/100 mL), and PABF (delta = 0.5 L/min) between inspiratory and expiratory breathhold measurements (P < 0.0001). Also, the MTT was significantly shorter (delta = -0.5 sec) at expiratory breathhold (P = 0.03). Inspiratory PBF and PBV showed a moderate correlation (r = 0.72 and 0.61, P < or = 0.008) with inspiratory PABF. CONCLUSION: Pulmonary perfusion during breathhold depends on the inspiratory level. Higher perfusion is observed at expiratory breathhold.

Focal gene induction in the liver of rats by a heat-inducible promoter using focused ultrasound hyperthermia: preliminary results.

OBJECTIVE: We sought to examine high-intensity focused ultrasound (HIFU)-induced hyperthermia in the liver of a rat model to focally induce green-fluorescent protein (GFP). MATERIALS AND METHODS: A total of 25 Copenhagen rats were included in this study. Rats were divided into groups treated with an adenovirus coding for green fluorescent protein (GFP) under the control of a hsp70B promoter and a CMV promoter. Ad-CMV-GFP-treated rats served as positive control. Untreated controls only subjected to MRI +/- HIFU-treatment served to find out optimal power of HIFU in the target area of the liver. Temperature was noninvasively monitored by temperature sensitive magnetic resonance imaging (MRI). RESULTS: Rats treated with Ad-hsp70B-GFP demonstrated localized gene induction within the liver parenchyma, in good correlation with MRI and histology. Applying an acoustic power of 1.92 W a relatively uniform focal temperature up to 42 +/- 5 degrees C within the liver parenchyma could be documented. 3 x 10(9) plaque-forming units proved to account for a very homogeneous liver infection. Number of fluorescent cells in the region of hyperthermia was similar to the control group treated with Ad-CMV-GFP. CONCLUSION: Using the introduced parameters spatially controlled gene induction within a parenchymal organ such as the liver in rats using HIFU under control of MRI is feasible.

[Measurements of respiratory motion using fast magnetic resonance imaging and inductively-coupled marker coils]. / Messungen der Atembewegung mit schneller Magnetresonanztomographie und induktiv gekoppelten Markerspulen.

The respiratory motion of the thoracic wall provides indirect information about the breathing displacement of the inner organs. To analyze the correlation between thoracic wall and lung motion for applications in radiation therapy, the breathing displacement of the lung is visualized with a fast gradient echo pulse sequence (trueFISP) at a rate of 2-3 images/sec. For quantification of the motion, a small inductively-coupled marker coil is attached to the chest wall and detected with a fast projection technique. Since the marker coil generates a flip angle amplification (factor 15) in its interior, very small nominal flip angles of 2 degrees can be used during the projection measurements which do not affect the image quality of the trueFISP images. Volunteer studies with the marker coil showed a good agreement with simultaneously acquired breathing belt data and position information extracted from the MR images. Whereas the breathing belt provided reliable data only within a certain dynamic range, the marker coil could detect also extreme breathing excursions with a precision better than 2 millimeters.

Fractionated stereotactic radiotherapy in low-grade astrocytomas: long-term outcome and prognostic factors.

PURPOSE: To evaluate outcome after fractionated stereotactic radiotherapy (RT) of patients with World Health Organization Grade 2 astrocytoma in terms of progression-free survival, overall survival, toxicity, quality of life, and prognostic factors. METHODS AND MATERIALS: Between 1984 and 2000, 143 patients with histologically proven Grade 2 astrocytoma were treated with fractionated stereotactic RT at our institution. The evaluation of the quality of life and toxicity was based on neurologic examinations and the Karnofsky performance score. Univariate analysis was performed on seven potential prognosticators and multivariate analysis on four prognosticators. RESULTS: The median follow-up was 44 months. The actuarial overall survival and progression-free survival was 58% and 39% at 5 years, respectively. Out-of-field recurrences occurred in 1 patient (1.2%). We did not observe a dose-response relationship. Overall survival and progression-free survival were significantly correlated with the absence of contrast media enhancement before RT (p <0.01). Toxicity was mild and included severe side effects of European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group Grade 3 in only 4 patients (2.8%). The Karnofsky performance score improved in most patients. CONCLUSION: Fractionated stereotactic RT is effective and has low toxicity in the treatment of Grade 2 gliomas. The rate of field border recurrences was not increased compared with after conventional RT. Exceeding the tumor dose did not improve the tumor control rate but did enhance toxicity. Pretherapeutic contrast media enhancement should be interpreted as a sign of higher grade tumor elements.

Analysis of intrathoracic tumor mobility during whole breathing cycle by dynamic MRI.

PURPOSE: To assess diaphragm, lung region, and tumor mobility during the whole breathing cycle using dynamic MRI. A generalized safety margin concept for radiotherapy planning was calculated and compared with an individualized concept. METHODS AND MATERIALS: The breathing cycles of 20 patients with solitary lung tumors (15 Stage I non-small-cell lung carcinoma, 5 small solitary metastases) were examined with dynamic MRI (true Fast imaging with steady precision, three images per second). The deep inspiratory and expiratory positions of the diaphragm, upper, middle, and lower lung regions, and the tumor were measured in three dimensions. The mobility of tumor-bearing and corresponding tumor-free regions was compared. Tumor mobility in quiet respiration served as an MRI-based safety margin concept. RESULTS: The motion of the lung regions was significantly greater in the lower regions than in the upper regions (5 +/- 2 cm vs. 0.9 +/- 0.4 cm, p < 0.05). Tumor-bearing lung regions showed a significantly lower mobility than the corresponding noninvolved regions (p < 0.05). In quiet respiration, tumor mobility showed a high variability; a safety margin of 3.4 mm in the upper, 4.5 mm in the middle, and 7.2 mm in the lower region was calculated. CONCLUSION: Dynamic MRI is a simple, noninvasive method to evaluate intrathoracic tumor mobility for therapy planning. Because of the high variability of tumor mobility, an individual safety margin is recommended.

Measurement of tumor diameter-dependent mobility of lung tumors by dynamic MRI.

BACKGROUND AND PURPOSE: To assess the influence of tumor diameter on tumor mobility and motion of the tumor bearing hemithorax during the whole breathing cycle in patients with stage I non-small-cell lung cancer (NSCLC) using dynamic MRI. PATIENTS AND METHODS: Breathing cycles of thirty-nine patients with solitary NSCLCs were examined using a trueFISP sequence (three images per second). Patients were divided into three groups according to the maximal tumor diameter in the transverse plane (<3, 3-5 and >5 cm). Continuous time-distance curves and deep inspiratory and expiratory positions of the chest wall, the diaphragm and the tumor were measured in three planes. Motion of tumor-bearing and corresponding contralateral non-tumor bearing regions was compared. RESULTS: Patients with a tumor >3 cm showed a significantly lower diaphragmatic motion of the tumor bearing compared with the non-tumor bearing hemithorax in the craniocaudal (CC) directions (tumors 3-5 cm: 23.4+/-1.2 vs 21.1+/-1.5 cm (P<0.05); tumors >5 cm: 23.4+/-1.2 vs 20.1+/-1.6 cm (P<0.01). Tumors >5 cm in the lower lung region showed a significantly lower mobility compared with tumors <3 cm (1.8+/-1.0 vs 3.8+/-0.7 cm, P<0.01) in the CC directions. CONCLUSIONS: Dynamic MRI is a simple non-invasive method to differentiate mobility of tumors with different diameters and its influence on the surrounding tissue. Tumor diameter has a significant influence on tumor mobility and this might be taken into account in future radiotherapy planning.