Accelerated Diffusion-Weighted Imaging in 3 T Breast MRI Using a Deep Learning Reconstruction Algorithm With Superresolution Processing: A Prospective Comparative Study.

OBJECTIVES: Diffusion-weighted imaging (DWI) enhances specificity in multiparametric breast MRI but is associated with longer acquisition time. Deep learning (DL) reconstruction may significantly shorten acquisition time and improve spatial resolution. In this prospective study, we evaluated acquisition time and image quality of a DL-accelerated DWI sequence with superresolution processing (DWI DL ) in comparison to standard imaging including analysis of lesion conspicuity and contrast of invasive breast cancers (IBCs), benign lesions (BEs), and cysts. MATERIALS AND METHODS: This institutional review board-approved prospective monocentric study enrolled participants who underwent 3 T breast MRI between August and December 2022. Standard DWI (DWI STD ; single-shot echo-planar DWI combined with reduced field-of-view excitation; b-values: 50 and 800 s/mm 2 ) was followed by DWI DL with similar acquisition parameters and reduced averages. Quantitative image quality was analyzed for region of interest-based signal-to-noise ratio (SNR) on breast tissue. Apparent diffusion coefficient (ADC), SNR, contrast-to-noise ratio, and contrast (C) values were calculated for biopsy-proven IBCs, BEs, and for cysts. Two radiologists independently assessed image quality, artifacts, and lesion conspicuity in a blinded independent manner. Univariate analysis was performed to test differences and interrater reliability. RESULTS: Among 65 participants (54 ± 13 years, 64 women) enrolled in the study, the prevalence of breast cancer was 23%. Average acquisition time was 5:02 minutes for DWI STD and 2:44 minutes for DWI DL ( P < 0.001). Signal-to-noise ratio measured in breast tissue was higher for DWI STD ( P < 0.001). The mean ADC values for IBC were 0.77 × 10 -3 ± 0.13 mm 2 /s in DWI STD and 0.75 × 10 -3 ± 0.12 mm 2 /s in DWI DL without significant difference when sequences were compared ( P = 0.32). Benign lesions presented with mean ADC values of 1.32 × 10 -3 ± 0.48 mm 2 /s in DWI STD and 1.39 × 10 -3 ± 0.54 mm 2 /s in DWI DL ( P = 0.12), and cysts presented with 2.18 × 10 -3 ± 0.49 mm 2 /s in DWI STD and 2.31 × 10 -3 ± 0.43 mm 2 /s in DWI DL . All lesions presented with significantly higher contrast in the DWI DL ( P < 0.001), whereas SNR and contrast-to-noise ratio did not differ significantly between DWI STD and DWI DL regardless of lesion type. Both sequences demonstrated a high subjective image quality (29/65 for DWI STD vs 20/65 for DWI DL ; P < 0.001). The highest lesion conspicuity score was observed more often for DWI DL ( P < 0.001) for all lesion types. Artifacts were scored higher for DWI DL ( P < 0.001). In general, no additional artifacts were noted in DWI DL . Interrater reliability was substantial to excellent (k = 0.68 to 1.0). CONCLUSIONS: DWI DL in breast MRI significantly reduced scan time by nearly one half while improving lesion conspicuity and maintaining overall image quality in a prospective clinical cohort.

Value of T2 Mapping MRI for Prostate Cancer Detection and Classification.

BACKGROUND: Currently, multi-parametric prostate MRI (mpMRI) consists of a qualitative T2 , diffusion weighted, and dynamic contrast enhanced imaging. Quantification of T2 imaging might further standardize PCa detection and support artificial intelligence solutions. PURPOSE: To evaluate the value of T2 mapping to detect prostate cancer (PCa) and to differentiate PCa aggressiveness. STUDY TYPE: Retrospective single center cohort study. POPULATION: Forty-four consecutive patients (mean age 67 years; median PSA 7.9 ng/mL) with mpMRI and verified PCa by subsequent targeted plus systematic MR/ultrasound (US)-fusion biopsy from February 2019 to December 2019. FIELD STRENGTH/SEQUENCE: Standardized mpMRI at 3 T with an additionally acquired T2 mapping sequence. ASSESSMENT: Primary endpoint was the analysis of quantitative T2 values and contrast differences/ratios (CD/CR) between PCa and benign tissue. Secondary objectives were the correlation between T2 values, ISUP grade, apparent diffusion coefficient (ADC) value, and PI-RADS, and the evaluation of thresholds for differentiating PCa and clinically significant PCa (csPCa). STATISTICAL TESTS: Mann-Whitney test, Spearman's rank (rs ) correlation, receiver operating curves, Youden's index (J), and AUC were performed. Statistical significance was defined as P < 0.05. RESULTS: Median quantitative T2 values were significantly lower for PCa in PZ (85 msec) and PCa in TZ (75 msec) compared to benign PZ (141 msec) or TZ (97 msec) (P < 0.001). CD/CR between PCa and benign PZ (51.2/1.77), respectively TZ (19.8/1.29), differed significantly (P < 0.001). The best T2 -mapping threshold for PCa/csPCa detection was for TZ 81/86 msec (J = 0.929/1.0), and for PZ 110 msec (J = 0.834/0.905). Quantitative T2 values of PCa did not correlate significantly with the ISUP grade (rs  = 0.186; P = 0.226), ADC value (rs  = 0.138; P = 0.372), or PI-RADS (rs  = 0.132; P = 0.392). DATA CONCLUSION: Quantitative T2 values could differentiate PCa in TZ and PZ and might support standardization of mpMRI of the prostate. Different thresholds seem to apply for PZ and TZ lesions. However, in the present study quantitative T2 values were not able to indicate PCa aggressiveness. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Visualization of the epimysium and fascia thoracolumbalis at the lumbar spine using MRI.

BACKGROUND: The fascia thoracolumbalis (FTL) is an important component for stabilization and motion control of the lumbar spine. It coordinates the traction forces of the autochthonous muscles of the back (AM) and connects them to the muscles of the abdominal wall, shoulder, and buttocks. OBJECTIVES: The aim of our study was to describe the assessment of the normal FTL and epimysium of the AM in MRI and to identify patterns associated with pathological changes in the lumbar spine. MATERIAL AND METHODS: A total of 33 patients were retrospectively evaluated: 15 patients had no pathology at the lumbar spine; six patients had previous hemilaminectomy, three had spondylodesis, two had ventrolisthesis, and seven had scoliosis. The thickness of the FTL and EM was measured, and the adhesion of both structures was assessed. RESULTS: The fascial thickness at the levels of the lumbar vertebral bodies LVB 3 was 1.8, of LVB 4 it was 2.0, of LVB 5 it was 2.1, and at the sacral vertebra SVB 1 it was 1.8 mm. Fascial adhesions together with thickening of the EM occurred at the level of LVB 4 in 36% of the cases independently of the underlying disorder. Only thickening of the EM was seen in 48% of cases at the level of SVB 1. By contrast, adhesion of the FTL without epimysial changes occurred in 36% of cases at the level of LVB 3. CONCLUSION: Thickening and adhesions at the EM and FTL occurred both postoperatively and in the case of scoliosis. Furthermore, lipomatous and muscular herniation could be detected in the FTL postoperatively. Epimysial and fascial alterations may be imaging manifestations of chronic myofascial back pain and should be included in radiological assessments.

[Diagnostic value of a 3D-SPACE-sequence with compressed sensing technology for the knee joint]. / Diagnostische Wertigkeit der 3­D-SPACE-Sequenz mit Compressed-sensing-Technologie am Kniegelenk.

BACKROUND: SPACE (3D fast spin echo acquisition) sequences require long scan times for three-dimensional assessment of acute injury of the knee joint and are flawed due to geometric blurring. Their implementation into routine diagnostic imaging was not feasible until recently. OBJECTIVES: By comparing conventional MRI (magnetic resonance imaging) sequences to 3D (three-dimensional) sequences, it was investigated whether the compressed sensing (CS) technique is inferior to the established 2D sequences with shorter examination times. MATERIALS AND METHODS: A total of 109 patients (age range 18-50 years) with knee injury were examined by MRI between April 2017 and May 2018. The inter- and intraobserver concordance of two blinded readers were assessed. Consensus was achieved in case of discrepancies. Descriptive analyses of absolute and relative frequency and distribution were tested by Fisher's exact test concerning differences between CS-SPACE and standard proton density fat suppressed imaging. RESULTS: Interoberserver concordance (IC) of conventional sequences before/after consensus amounted to 58.8/68.1% (medial meniscus, MM), 68.8/88.7% (lateral meniscus, LM) 88.9/97.2% (anterior cruciate ligament, ACL), 99/100% (posterior cruciate ligament, PCL), 88.9/97.2% (collateral ligament, CL) and chondral injury (CI) 1-2: 64.2%, CI-3: 77% and CI-4: 76%. The IC of CS-SPACE amounted before/after consensus of MM to 50.4/77%, LM 68.8/88%, ACL 89.9/94.5%, PCL 97.2/99.0%, CL 92.6/96.3%. IC of CI was evaluated without consensus and amounted to 65.1% (CI 1-2), 66% (CI 3) and 81.6% (CI 4). CONCLUSIONS: Injuries of ACL, PCL and CL have excellent IC between 3D and 2D sequences. Excellent IC could be found in CI grade 3 and 4 when using 2D sequences and CI grade 4 utilizing CS-SPACE. Our results indicate that CS-SPACE is useful in diagnosing acute knee injuries.

Advanced Diffusion-Weighted Abdominal Imaging: Qualitative and Quantitative Comparison of High and Ultra-High b-Values for Lesion Detection and Image Quality.

INTRODUCTION: Magnetic resonance imaging (MRI) of the abdomen increasingly incorporates diffusion-weighted imaging (DWI) sequences. Whereas DWI can substantially aid in detecting and characterizing suspicious findings, it remains unclear to what extent the use of ultra-high b-value DWI might further be of aid for the radiologist especially when using DWI sequences with advanced processing. The target of this study was therefore to compare high and ultra-high b-value DWI in abdominal MRI examinations. METHODS: This institutional review board-approved, prospective study included abdominal MRI examinations of 70 oncologic patients (mean age, 58 years; range, 21-90 years) examined with a clinical 1.5 T MRI scanner (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) with an advanced echo planar DWI sequence (b = 0, 50, 900, and 1500 s/mm) after ex vivo phantom and in vivo volunteer investigations. High b900 and ultra-high b1500 DWIs were compared by a qualitative reading for image quality and lesion conspicuity using a 5-point Likert scale with 2 radiologists as readers. The ratios of apparent signal intensities of suspicious lesions/normal tissue of the same organ (LNTRs) were calculated. Appropriate methods were used for statistical analysis, including Wilcoxon signed-rank test and κ statistic for interreader agreement analysis (P < 0.05/0.0125/0.005 after Bonferroni correction). RESULTS: Image quality was significantly increased with b900 as compared with b1500 DWI (P < 0.001) despite using an advanced DWI sequence. A total of 153 suspicious lesions were analyzed. Overall reader confidence for characterization/detection of malignant lesions and, correspondingly, the LNTR (mean, 2.7 ± 1.8 vs 2.4 ± 1.6) were significantly higher with b900 than with b1500 DWI (P < 0.001 and P < 0.001). The increased confidence of lesion recognition and LNTR in the b900 DWI remained significant qualitatively in lymphatic and hepatic lesions and quantitatively in lymphatic, pulmonal, and osseous lesions. CONCLUSIONS: Using high b-value DWI (900 s/mm) provided an improved image quality and also lesion conspicuity as compared with ultra-high b-value DWI (1500 s/mm) in oncologic abdominal examinations despite using advanced processing. Consequently, the value for additional ultra-high b-value DWI in oncologic examinations should be critically evaluated in future studies.

Image Quality Assessment of 2D versus 3D T2WI and Evaluation of Ultra-high b-Value (b=2,000 mm/s2) DWI for Response Assessment in Rectal Cancer.

AIM: The purpose of this IRB-approved, retrospective study was to compare image quality between 2D and high-resolution 3D, T2-weighted (T2WI) magnetic resonance imaging (MRI) sequences and to investigate the additional value of ultra-high b-value diffusion-weighted imaging (DWI; b=2,000 mm/s2) for both rectal cancer staging and evaluating treatment response. MATERIALS AND METHODS: From 12 February to 24 August 2016, 26 consecutive patients (22 males, four females; mean age: 61.9±14.0 years) with histologically-proven rectal cancer. In total 31 examinations [12 prior to and 19 after chemoradiation (CRT)] were included. The patients underwent pelvic MRI on a 3.0-T scanner (Magnetom Skyra, Erlangen, Germany). Three radiologists (3, 4, and 5 years of experience in MRI, respectively) independently assessed all images and rated the image quality of DWI (b=800 mm/s2), apparent diffusion coefficient map, DWI (b=2,000 mm/s2), 3D sagittal T2WI, 3D axial T2WI, 2D sagittal T2WI, and 2D axial T2WI of each patient, respectively. In addition, signal intensity ratios (SIR) were calculated between rectal cancer and obturator internus muscle (background) in all patients after CRT on DWI (b=2,000 mm/s2) and correlated with histopathological regression grade (RG). RESULTS: Tumor delineation was significantly better by 2D T2WI than 3D T2WI both before and after CRT (before CRT: Z=-3.2, p=0.02; after CRT: Z=-4.408, p<0.001; all: Z=-5.192; p<0.001) and was the preferred method, although image quality ratings were not significantly different (3D sagittal: 4.00±0.48; 2D sagittal: 4.03±0.34, p=0.713; 3D axial: 3.85±0.61, 2D axial: 3.78±0.64, p=0.537). Independent t-test showed significantly higher SIR between those with RG 1 or 2 (moderate response: mean score=2.02) and those with RG 3+4 (good response: mean score=0.8) (t=3.044, p=0.011). In those with RG 4 (complete response), SIR of b2000 was 0.946 compared to a 1.41 average of the whole cohort. In two patients, tumor was invisible on b2000 following CRT (RG 3 and 4, respectively). Interobserver agreement was mostly good (κ≥0.6) regarding image quality assessment, except for poor agreement (κ=0.4) in DWI (b2000) between the two less-experienced readers. CONCLUSION: In conclusion, 3D T2WI might be useful for evaluating response to neoadjuvant therapy in a comprehensive, cost-effective protocol, where 2D imaging seems to be preferable. In addition, DWI (b2000) may be beneficial in assessing both the primary and the residual tumor after CRT in rectal cancer and SIR may be helpful in assessing response to CRT.

Real-time cardiac magnetic resonance cine imaging with sparse sampling and iterative reconstruction for left-ventricular measures: Comparison with gold-standard segmented steady-state free precession.

BACKGROUND: Segmented cine imaging with a steady-state free-precession sequence (Cine-SSFP) is currently the gold standard technique for measuring ventricular volumes and mass, but due to multi breath-hold (BH) requirements, it is prone to misalignment of consecutive slices, time consuming and dependent on respiratory capacity. Real-time cine avoids those limitations, but poor spatial and temporal resolution of conventional sequences has prevented its routine application. We sought to examine the accuracy and feasibility of a newly developed real-time sequence with aggressive under-sampling of k-space using sparse sampling and iterative reconstruction (Cine-RT). METHODS: Stacks of short-axis cines were acquired covering both ventricles in a 1.5T system using gold standard Cine-SSFP and Cine-RT. Acquisition parameters for Cine-SSFP were: acquisition matrix of 224×196, temporal resolution of 39ms, retrospective gating, with an average of 8 heartbeats per slice and 1-2 slices/BH. For Cine-RT: acquisition matrix of 224×196, sparse sampling net acceleration factor of 11.3, temporal resolution of 41ms, prospective gating, real-time acquisition of 1 heart-beat/slice and all slices in one BH. LV contours were drawn at end diastole and systole to derive LV volumes and mass. RESULTS: Forty-one consecutive patients (15 male; 41±17years) in sinus rhythm were successfully included. All images from Cine-SSFP and Cine-RT were considered to have excellent quality. Cine-RT-derived LV volumes and mass were slightly underestimated but strongly correlated with gold standard Cine-SSFP. Inter- and intra-observer analysis presented similar results between both sequences. CONCLUSIONS: Cine-RT featuring sparse sampling and iterative reconstruction can achieve spatial and temporal resolution equivalent to Cine-SSFP, providing excellent image quality, with similar precision measurements and highly correlated and only slightly underestimated volume and mass values.

Comparison of myocardial T1 and T2 values in 3 T with T2* in 1.5 T in patients with iron overload and controls.

Myocardial iron quantification remains limited to 1.5 T systems with T2* measurement. The present study aimed at comparing myocardial T2* values at 1.5 T to T1 and T2 mapping at 3.0 T in patients with iron overload and healthy controls. A total of 17 normal volunteers and seven patients with a history of myocardial iron overload were prospectively enrolled. Mid-interventricular septum T2*, native T1 and T2 times were quantified on the same day, using a multi-echo gradient-echo sequence at 1.5 T and T1 and T2 mapping sequences at 3.0 T, respectively. Subjects with myocardial iron overload (T2* < 20 ms) in comparison with those without had significantly lower mean myocardial T1 times (868.9 ± 120.2 vs. 1170.3 ± 25.0 ms P = 0.005 respectively) and T2 times (34.9 ± 4.7 vs. 45.1 ± 2.0 ms P = 0.007 respectively). 3 T T1 and T2 times strongly correlated with 1.5 T, T2* times (Pearson's r = 0.95 and 0.91 respectively). T1 and T2 measures presented less variability than T2* in inter- and intra-observer analysis. Native myocardial T1 and T2 times at 3 T correlate closely with T2* times at 1.5 T and may be useful for myocardial iron overload quantification.

Feasibility study of computed vs measured high b-value (1400 s/mm²) diffusion-weighted MR images of the prostate.

AIM: To evaluate the impact of computed b = 1400 s/mm(2) (C-b1400) vs measured b = 1400 s/mm(2) (M-b1400) diffusion-weighted images (DWI) on lesion detection rate, image quality and quality of lesion demarcation using a modern 3T-MR system based on a small-field-of-view sequence (sFOV). METHODS: Thirty patients (PSA: 9.5 ± 8.7 ng/mL; 68 ± 12 years) referred for magnetic resonance imaging (MRI) of the prostate were enrolled in this study. All measurements were performed on a 3T MR system. For DWI, a single-shot EPI diffusion sequence (b = 0, 100, 400, 800 s/mm²) was utilized. C-b1400 was calculated voxelwise from the ADC and diffusion images. Additionally, M-b1400 was acquired for evaluation and comparison. Lesion detection rate and maximum lesion diameters were obtained and compared. Image quality and quality of lesion demarcation were rated according to a 5-point Likert-type scale. Ratios of lesion-to-bladder as well as prostate-to-bladder signal intensity (SI) were calculated to estimate the signal-to-noise-ratio (SNR). RESULTS: Twenty-four lesions were detected on M-b1400 images and compared to C-b1400 images. C-b1400 detected three additional cancer suspicious lesions. Overall image quality was rated significantly better and SI ratios were significantly higher on C-b1400 (2.3 ± 0.8 vs 3.1 ± 1.0, P < 0.001; 5.6 ± 1.8 vs 2.8 ± 0.9, P < 0.001). Comparison of lesion size showed no significant differences between C- and M-b1400 (P = 0.22). CONCLUSION: Combination of a high b-value extrapolation and sFOV may contribute to increase diagnostic accuracy of DWI without an increase of acquisition time, which may be useful to guide targeted prostate biopsies and to improve quality of multiparametric MRI (mMRI) especially under economical aspects in a private practice setting.

Areas suspicious for prostate cancer: MR-guided biopsy in patients with at least one transrectal US-guided biopsy with a negative finding--multiparametric MR imaging for detection and biopsy planning.

PURPOSE: To prospectively investigate the incremental value of multiparametric magnetic resonance (MR) imaging compared with standard T2-weighted imaging for biopsy planning. MATERIALS AND METHODS: The study was approved by the institutional review board; informed consent was obtained. Consecutive patients underwent T2-weighted imaging supplemented with multiparametric 1.5-T MR imaging, consisting of hydrogen 1 ((1)H) MR spectroscopy, diffusion-weighted (DW) imaging, and contrast material-enhanced MR imaging. Quantitative parameters were calculated: (choline plus creatine)-to-citrate ratio, apparent diffusion coefficient, and volume transfer constant and exchange rate constant. The prostate was divided into 20 standardized areas. Each area was classified as benign, inconclusive, or suspicious at T2-weighted imaging, followed by quantitative evaluation of all inconclusive and suspicious areas with multiparametric MR imaging. MR-guided biopsy was performed in lesions classified as suspicious for cancer with at least one of the techniques after transfer to three-dimensional T2-weighted images. Diagnostic parameters were calculated on a per-lesion and per-patient basis for all combinations of T2-weighted imaging with multiparametric MR imaging. RESULTS: Fifty-four patients had a median of two prior transrectal ultrasonographic biopsies with negative findings. Each patient had a median of three suspicious lesions. Prostate cancer was demonstrated in 21 of 54 patients. Biopsy was performed in 178 lesions; 53 were positive for prostate cancer. Detection rates and test negative results, respectively, were as follows: T2-weighted imaging, 70% and 50%; T2-weighted imaging and (1)H MR spectroscopy, 81% and 32%; T2-weighted imaging and contrast-enhanced MR imaging, 83% and 29%; T2-weighted imaging and DW imaging, 85% and 30%; T2-weighted imaging, (1)H MR spectroscopy, and contrast-enhanced MR imaging, 91% and 13%; T2-weighted imaging, (1)H MR spectroscopy, and DW imaging, 94% and 15%; T2-weighted imaging, DW imaging, and contrast-enhanced MR imaging, 94% and 13%; T2-weighted imaging, (1)H MR spectroscopy, DW imaging, and contrast-enhanced MR imaging, 100% and 0%. CONCLUSION: Only the combination of T2-weighted imaging with all three multiparametric techniques depicts all identifiable prostate cancers; a double combination with DW imaging and (1)H MR spectroscopy or contrast-enhanced MR imaging misses 6%, while reasonably reducing the number of areas needing biopsy.

Simulation-based comparison of two approaches frequently used for dynamic contrast-enhanced MRI.

PURPOSE: The purpose was to compare two approaches for the acquisition and analysis of dynamic-contrast-enhanced MRI data with respect to differences in the modelling of the arterial input-function (AIF), the dependency of the model parameters on physiological parameters and their numerical stability. Eight hundred tissue concentration curves were simulated for different combinations of perfusion, permeability, interstitial volume and plasma volume based on two measured AIFs and analysed according to the two commonly used approaches. The transfer constants (Approach 1) K (trans) and (Approach 2) k (ep) were correlated with all tissue parameters. K (trans) showed a stronger dependency on perfusion, and k (ep) on permeability. The volume parameters (Approach 1) v (e) and (Approach 2) A were mainly influenced by the interstitial and plasma volume. Both approaches allow only rough characterisation of tissue microcirculation and microvasculature. Approach 2 seems to be somewhat more robust than 1, mainly due to the different methods of CA administration.

Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors.

PURPOSE: BIBF 1120 is an oral, potent angiokinase inhibitor targeting receptors of the vascular endothelial growth factors, platelet-derived growth factors, and fibroblast growth factors. This phase I, accelerated titration study assessed the maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamic effects of BIBF 1120. PATIENTS AND METHODS: Sixty-one patients with advanced cancers received BIBF 1120 in successive cohorts. Twenty-five received 50 to 450 mg once daily and 36 received 150 to 300 mg twice daily in 4-week treatment courses interspersed by 1 week of washout. Dynamic contrast-enhanced magnetic resonance imaging assessed antiangiogenic effect in 42 patients. RESULTS: Most frequent BIBF 1120-related adverse events were mostly mild to moderate (Common Toxicity Criteria grade 1-2) nausea (68.9%), vomiting (45.9%), and diarrhea (44.3%). The majority of dose-limiting adverse events of Common Toxicity Criteria grade 3 or 4 were reversible liver enzyme elevations. The maximum tolerated dose was 250 mg of BIBF 1120 for once and twice daily dosing. BIBF 1120 was absorbed moderately fast (t(max) = 1-3 hours at steady state), with no deviation from dose linearity and no decrease of exposure over time. The gMean terminal half-life was from 13 to 19 hours. One complete and two partial responses occurred in patients with renal cell cancer (n = 2) and colorectal cancer (n = 1). Dynamic contrast-enhanced magnetic resonance imaging showed a significant reduction in tumor blood flow in 55% of evaluable patients. CONCLUSIONS: BIBF 1120 dosed continuously displayed a favorable safety and pharmacokinetics profile, and first efficacy signals were observed. Twice daily dosing permitted increased drug exposure without additional toxicity. Two hundred milligrams BIBF 1120 twice daily is the recommended dose for phase II monotherapy studies.

Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging.

PURPOSE: To assess vascular remodeling in tumors during two different antiangiogenic therapies with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging and to evaluate the vessel size index (VSI) as a novel biomarker of therapy response. MATERIALS AND METHODS: In two independent experiments, nude mice bearing human skin squamous cell carcinoma xenografts were treated with a vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or a multitargeted tyrosine kinase inhibitor (SU11248). Changes in tumor vascularity were assessed by DCE-MRI and vessel size imaging. DCE-MRI data were analyzed applying a two-compartment model (Brix), calculating the parameters Amplitude and k(ep). RESULTS: For both experiments Amplitude decreased significantly in treated tumors while k(ep) did not change significantly. VSI showed controversial results. VSI was significantly increased in SU11248-treated A431 tumors, whereas no changes were found in bevacizumab-treated HaCaT-ras-A-5RT3 tumors. Immunohistology confirmed these results and suggest differences in the maturation of tumor vascularization as a possible explanation. CONCLUSION: DCE-MRI and vessel size imaging provide reliable and supplementing biomarkers of antiangiogenic therapy response. The results of both methods are in excellent agreement with histology. Nevertheless, our results also indicate that vascular remodeling is complex and that a uniform response cannot be expected for different tumors and therapies.

Metronomic antiangiogenic therapy with capecitabine and celecoxib in advanced tumor patients--results of a phase II study.

BACKGROUND: Combined therapy of continuous low dose capecitabine and high dose celecoxib targeting angiogenesis was used in a phase II trial to treat advanced cancer patients. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to monitor antiangiogenic effects. MATERIAL AND METHODS: 37 Patients (21 men, 16 women), mean age 60 years, with advanced and progressive cancer of various tumor types were included. Therapy consisted of 2 x 500 mg oral capecitabine/ day and 2 x 400 mg oral celecoxib/day continuously until progression of disease. To monitor antiangiogenic effects, DCE-MRI measurements were performed at baseline, after 1 month, and after 3 months of therapy. Tumor assessment was performed according to RECIST criteria, toxicity was evaluated according to the CTC version 2.0 catalogue. RESULTS: Therapy was well tolerated without grade 3 and 4 toxicities. The mean number of treatment cycles was 4 (range: 1-15+). Disease stabilization after 3 cycles was seen in 11 patients. 6 patients were stable over long periods. The mean number of treatment cycles in this group was 10 (range: 7-15+). DCE-MRI demonstrated a reduction of tumor vessel permeability and blood flow in patients who reached stable disease or some minor regression. CONCLUSION: Continuous dosing of the combination of capecitabine and celecoxib was well tolerated, produced antiangiogenic effects, and has antitumor activity. Patients with rapid progression did not benefit.

Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors.

PURPOSE: AZD2171 is a highly potent oral selective inhibitor of vascular endothelial growth factor (VEGF) signaling. This phase I study was designed to evaluate the safety and tolerability of increasing doses of AZD2171, with additional assessments of pharmacokinetics, pharmacodynamics, and efficacy. PATIENTS AND METHODS: In part A, 36 patients with solid tumors and liver metastases refractory to standard therapies received once-daily oral AZD2171 (0.5 to 60 mg). Doses were escalated in successive cohorts until the maximum-tolerated dose was identified. In part B, patients with (n = 36) or without (n = 11) liver metastases were randomly assigned to receive once-daily AZD2171 (20, 30, or 45 mg). In both parts, treatment continued until tumor progression or dose-limiting toxicity (DLT) was observed. RESULTS: Eighty-three patients received AZD2171, which was generally well tolerated at doses of 45 mg/d or less; the most frequently reported dose-related adverse events were diarrhea, dysphonia, and hypertension. The most common DLT was hypertension (n = 7), which occurred at AZD2171 doses of 20 mg and higher. After a single dose, maximum plasma (peak) drug concentration after single-dose administration (Cmax) was achieved 1 to 8 hours postdosing with an arithmetic mean half-life associated with terminal slope of a semilogarithmic concentration-time curve (t1/2 lamda(z)) of 22 hours. Pharmacodynamic assessments demonstrated time-, dose-, and exposure-related decreases in initial area under the curve, defined over 60 seconds post-contrast arrival in the tissue (iAUC60) using dynamic contrast-enhanced magnetic resonance imaging, as well as dose- and time-dependent reductions in soluble VEGF receptor 2 levels. Preliminary evidence of efficacy included two confirmed partial responses and 22 patients with stable disease; effects on tumor size appeared to be dose related. CONCLUSION: Once-daily oral AZD2171 at doses of 45 mg or less was generally well tolerated and was associated with encouraging antitumor activity in patients with a broad range of advanced solid tumors.

Autoalignment of intervertebral disks.

PURPOSE: To develop an automated planning method to obtain double oblique slices for clinically relevant diagnoses of spine-related pathologies. MATERIALS AND METHODS: Thirty healthy volunteers, 18 patients with cervical spine (c-spine) pathologies, and 15 patients with lumbar spine (l-spine) pathologies were included in this study. The planning method requires no interaction and is calculated online on the MR scanner after two sagittal acquisitions (a MR myelogram and standard T2-weighted (T2W) acquisition). The planning of the subsequent double oblique slice packets is calculated automatically. The results from the volunteers were evaluated visually by an operating technician. The results obtained in a clinical trial from interactive planning by an operating technician and from automated planning were compared. RESULTS: Visual assessment of the planned slices in the T2W images of all subjects confirmed the accuracy and robustness of the method for both applications. The differences in positions and orientations between interactively and automatically planned transverse series were within the range of interindividual variability. CONCLUSION: he new approach can be used to automatically plan double oblique MR images for examination of spine-related pathologies with high reliability and robustness. The major advantage is that simultaneous planning in the transversal-coronal and transversal-sagittal orientations can be performed without any additional measurement. Another advantage is that standardized localization of the nerve roots in the center of the image can be obtained.

Hemodynamical assessment of cavernous hemangioma in cavernous sinus using MR-DSA and conventional DSA.

We report a hemodynamical assessment of the blood turnover pattern as well as the imaging of cavernous hemangioma in a cavernous sinus using time-resolved contrast enhanced 2D projection MRA, also known as MR-DSA, and conventional digital subtraction angiography (DSA), before and after radiotherapy. MR-DSA showed very fast dynamical images of a contrast turnover pattern and was well matched with the findings obtained from DSA. MR-DSA is a non-invasive study, and can replace DSA in examining a vascular tumor for the initial work-up and follow-up examination.

Dynamic contrast enhancement of paragangliomas of the head and neck: evaluation with time-resolved 2D MR projection angiography.

Our objective was to evaluate tumor hemodynamics of paragangliomas of the head and neck. A 2D magnetic resonance projection angiography (MRPA) protocol was developed. Six patients with histologically proven paragangliomas were included in the study. The sequence protocol and data post-processing procedure were optimized in view of a high temporal resolution and maximum contrast-to-noise ratio. Image-time series of two freely orientated slabs could be obtained. Correlation analysis was performed to generate selective arterial and venous weighted angiographic images. Glomus tumors showed a rapid and intense homogeneous enhancement following the intravenous administration of contrast material. The smallest tumors investigated measured 10 mm and could be visualized clearly. Time-resolved analysis of the tumor enhancement revealed an early bolus arrival within the vascular bed of the tumor and prolonged incomplete washout indicating blood pooling. The dynamic contrast enhancement of glomus tumors can be evaluated non-invasively with MRPA providing a high temporal resolution and high image quality. The characteristic contrast enhancement of glomus tumors can be helpful in the diagnostic workup of lesions that may mimic glomus tumors.

Assessment of pulmonary perfusion with ultrafast projection magnetic resonance angiography in comparison with lung perfusion scintigraphy in patients with malignant stenosis.

RATIONALE AND OBJECTIVE: The aim of this study was to demonstrate and measure perfusion deficits caused by central bronchogenic carcinoma and to compare magnetic resonance angiography (MRA) perfusion data with data of perfusion scintigraphy. The diagnostic value of 2D MRA in detection of malignant pulmonary artery stenosis in comparison with conventional DSA was investigated. MATERIALS AND METHODS: Eighteen patients were included in the study. MRA, conventional pulmonary angiograms, and pulmonary perfusion scintigrams were performed. MRA and DSA were compared and MR pulmonary perfusion data were assessed and compared with scintigraphical data. RESULTS: Perfusion defect could be demonstrated and localized in all patients. A quantitative perfusion deficit and a side dependent perfusion ratio could be evaluated. There was statistically significant correlation between MR perfusion and scintigraphically acquired data. 2D MRA showed a high correlation for detection and grading of stenosis compared with angiograms. CONCLUSIONS: Pulmonary perfusion could be demonstrated by using an ultrafast 2D projection MR DSA sequence. This technique allows measurement and quantification of pulmonary perfusion abnormalities in patients with malignant stenosis with statistically significant correlation to perfusion scintigraphy. The diagnostic potency in the evaluation of malignant pulmonary artery stenosis compared with conventional DSA could be shown.

Non-invasive follow-up evaluation of post-embolized AVM with time-resolved MRA: a case report.

We report the hemodynamic assessment in a patient with cerebral arteriovenous malformation using time-resolved magnetic resonance angiography (TRMRA), a non-invasive modality, and catheter-based digital subtraction angiography (DSA), before and after embolization. Comparison of the results showed that TR-MRA produced very fast dynamic images and the findings closely matched those obtained at DSA. For initial work-up and follow-up studies in patients with vascular lesions, TR-MRA and DSA are therefore comparable.