TY  - JOUR
AB  - OBJECTIVES: The UK Biobank (UKBB) and German National Cohort (NAKO) are among the largest cohort studies, capturing a wide range of health-related data from the general population, including comprehensive magnetic resonance imaging (MRI) examinations. The purpose of this study was to demonstrate how MRI data from these large-scale studies can be jointly analyzed and to derive comprehensive quantitative image-based phenotypes across the general adult population. MATERIALS AND METHODS: Image-derived features of abdominal organs (volumes of liver, spleen, kidneys, and pancreas; volumes of kidney hilum adipose tissue; and fat fractions of liver and pancreas) were extracted from T1-weighted Dixon MRI data of 17,996 participants of UKBB and NAKO based on quality-controlled deep learning generated organ segmentations. To enable valid cross-study analysis, we first analyzed the data generating process using methods of causal discovery. We subsequently harmonized data from UKBB and NAKO using the ComBat approach for batch effect correction. We finally performed quantile regression on harmonized data across studies providing quantitative models for the variation of image-derived features stratified for sex and dependent on age, height, and weight. RESULTS: Data from 8791 UKBB participants (49.9% female; age, 63 ± 7.5 years) and 9205 NAKO participants (49.1% female, age: 51.8 ± 11.4 years) were analyzed. Analysis of the data generating process revealed direct effects of age, sex, height, weight, and the data source (UKBB vs NAKO) on image-derived features. Correction of data source-related effects resulted in markedly improved alignment of image-derived features between UKBB and NAKO. Cross-study analysis on harmonized data revealed comprehensive quantitative models for the phenotypic variation of abdominal organs across the general adult population. CONCLUSIONS: Cross-study analysis of MRI data from UKBB and NAKO as proposed in this work can be helpful for future joint data analyses across cohorts linking genetic, environmental, and behavioral risk factors to MRI-derived phenotypes and provide reference values for clinical diagnostics.
AU  - Gatidis, S.*
AU  - Kart, T.*
AU  - Fischer, M.*
AU  - Winzeck, S.*
AU  - Glocker, B.*
AU  - Bai, W.*
AU  - Bülow, R.*
AU  - Emmel, C.*
AU  - Friedrich, L.*
AU  - Kauczor, H.U.*
AU  - Keil, T.*
AU  - Kröncke, T.*
AU  - Mayer, P.*
AU  - Niendorf, T.*
AU  - Peters, A.
AU  - Pischon, T.*
AU  - Schaarschmidt, B.M.*
AU  - Schmidt, B.*
AU  - Schulze, M.B.*
AU  - Umutle, L.*
AU  - Völzke, H.*
AU  - Küstner, T.*
AU  - Bamberg, F.*
AU  - Schölkopf, B.*
AU  - Rueckert, D.*
C1  - 67584
C2  - 53553
CY  - Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
SP  - 346-354
TI  - Better Together: Data harmonization and cross-study analysis of abdominal MRI data from UK Biobank and the German National Cohort.
JO  - Invest. Radiol.
VL  - 58
IS  - 5
PB  - Lippincott Williams & Wilkins
PY  - 2023
SN  - 0020-9996
ER  - 

TY  - JOUR
AB  - BACKGROUND: Reproducible image quality is of high relevance for large cohort studies and can be challenging for magnetic resonance imaging (MRI). Automated image quality assessment may contribute to conducting radiologic studies effectively. PURPOSE: The aims of this study were to assess protocol repetition frequency in population-based whole-body MRI along with its effect on examination time and to examine the applicability of automated image quality assessment for predicting decision-making regarding repeated acquisitions. MATERIALS AND METHODS: All participants enrolled in the prospective, multicenter German National Cohort (NAKO) study who underwent whole-body MRI at 1 of 5 sites from 2014 to 2016 were included in this analysis (n = 11,347). A standardized examination program of 12 protocols was used. Acquisitions were carried out by certified radiologic technologists, who were authorized to repeat protocols based on their visual perception of image quality. Eleven image quality parameters were derived fully automatically from the acquired images, and their discrimination ability regarding baseline acquisitions and repetitions was tested. RESULTS: At least 1 protocol was repeated in 12% (n = 1359) of participants, and more than 1 protocol in 1.6% (n = 181). The repetition frequency differed across protocols (P < 0.001), imaging sites (P < 0.001), and over the study period (P < 0.001). The mean total scan time was 62.6 minutes in participants without and 67.4 minutes in participants with protocol repetitions (mean difference, 4.8 minutes; 95% confidence interval, 4.5-5.2 minutes). Ten of the automatically derived image quality parameters were individually retrospectively predictive for the repetition of particular protocols; for instance, "signal-to-noise ratio" alone provided an area under the curve of 0.65 (P < 0.001) for repetition of the Cardio Cine SSFP SAX protocol. Combinations generally improved prediction ability, as exemplified by "image sharpness" plus "foreground ratio" yielding an area under the curve of 0.89 (P < 0.001) for repetition of the Neuro T1w 3D MPRAGE protocol, versus 0.85 (P < 0.001) and 0.68 (P < 0.001) as individual parameters. CONCLUSIONS: Magnetic resonance imaging protocol repetitions were necessary in approximately 12% of scans even in the highly standardized setting of a large cohort study. Automated image quality assessment shows predictive value for the technologists' decision to perform protocol repetitions and has the potential to improve imaging efficiency.
AU  - Schuppert, C.*
AU  - von Krüchten, R.*
AU  - Hirsch, J.G.*
AU  - Rospleszcz, S.
AU  - Hoinkiss, D.C.*
AU  - Selder, S.*
AU  - Köhn, A.*
AU  - von Stackelberg, O.*
AU  - Peters, A.
AU  - Völzke, H.*
AU  - Kröncke, T.*
AU  - Niendorf, T.*
AU  - Forsting, M.*
AU  - Hosten, N.*
AU  - Hendel, T.
AU  - Pischon, T.*
AU  - Jöckel, K.H.*
AU  - Kaaks, R.*
AU  - Bamberg, F.*
AU  - Kauczor, H.U.*
AU  - Günther, M.*
AU  - Schlett, C.L.*
C1  - 64342
C2  - 52195
SP  - 478-487
TI  - Whole-body magnetic resonance imaging in the large population-based German National Cohort study: Predictive capability of automated image quality assessment for protocol repetitions.
JO  - Invest. Radiol.
VL  - 57
IS  - 7
PY  - 2022
SN  - 0020-9996
ER  - 

TY  - JOUR
AB  - Introduction Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls. Materials and Methods Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement. Magnetic resonance features were summarized in a phenotypic-based score (range, 0-6). Univariate, multivariate correlation, and unsupervised clustering were performed. Results Among 243 subjects with complete multiorgan MR data sets included in the analysis (55.6 ± 8.9 years, 62% males), 48 were classified as subjects with prediabetes and 38 as subjects with diabetes. The MR phenotypic score was significantly higher in subjects with prediabetes and diabetes as compared with controls (mean score, 3.00 ± 1.04 and 2.69 ± 0.98 vs 1.22 ± 0.98, P < 0.001 respectively), also after adjustment for potential confounders. We identified 2 clusters of MR phenotype patterns associated with glycemic status (P < 0.001), independent of the MR score (cluster II-metabolic specific: odds ratio, 2.49; 95% CI, 1.00-6.17; P = 0.049). Discussion Subjects with prediabetes and diabetes have a significantly higher phenotypic-based score with a distinctive multiorgan phenotypic pattern, which may enable improved disease characterization.
AU  - Storz, C.*
AU  - Rospleszcz, S.
AU  - Lorbeer, R.*
AU  - Hetterich, H.*
AU  - Auweter, S.D.*
AU  - Sommer, W.*
AU  - Machann, J.
AU  - Gatidis, S.*
AU  - Rathmann, W.*
AU  - Heier, M.
AU  - Linkohr, B.
AU  - Meisinger, C.
AU  - Reiser, M.*
AU  - Hoffmann, U.*
AU  - Peters, A.
AU  - Schlett, C.L.*
AU  - Bamberg, F.*
C1  - 53545
C2  - 44617
SP  - 357-364
TI  - Phenotypic multiorgan involvement of subclinical disease as quantified by magnetic resonance imaging in subjects with prediabetes, diabetes, and normal glucose tolerance.
JO  - Invest. Radiol.
VL  - 53
IS  - 6
PY  - 2018
SN  - 0020-9996
ER  - 

TY  - JOUR
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic value of x-ray dark-field imaging in projection radiography-based depiction of pneumothoraces in the neonatal murine lung, a potentially life-threatening medical condition that requires a timely and correct diagnosis. MATERIALS AND METHODS: By the use of a unique preclinical model, 7-day-old C57Bl/6N mice received mechanical ventilation for 2 or 8 hours with oxygen-rich gas (FIO2 = 0.4; n = 24). Unventilated mice either spontaneously breathed oxygen-rich gas (FIO2 = 0.4) for 2 or 8 hours or room air (n = 22). At the end of the experiment, lungs were inflated with a standardized volume of air after a lethal dose of pentobarbital was administered to the pups. All lungs were imaged with a prototype grating-based small-animal scanner to acquire x-ray transmission and dark-field radiographs. Image contrast between the air-filled pleural space and lung tissue was quantified for both transmission and dark-field radiograms. After the independent expert's assessment, 2 blinded readers evaluated all dark-field and transmission images for the presence or absence of pneumothoraces. Contrast ratios, diagnostic accuracy, as well as reader's confidence and interreader agreement were recorded for both imaging modalities. RESULTS: Evaluation of both x-ray transmission and dark-field radiographs by independent experts revealed the development of a total of 10 pneumothoraces in 8 mice. Here, the contrast ratio between the air-filled pleural space of the pneumothoraces and the lung tissue was significantly higher in the dark field (8.4 ± 3.5) when compared with the transmission images (5.1 ± 2.8; P < 0.05). Accordingly, the readers' diagnostic confidence for the diagnosis of pneumothoraces was significantly higher for dark-field compared with transmission images (P = 0.001). Interreader agreement improved from moderate for the analysis of transmission images alone (κ = 0.41) to very good when analyzing dark-field images alone (κ = 0.90) or in combination with transmission images (κ = 0.88). Diagnostic accuracy significantly improved for the analysis of dark-field images alone (P = 0.04) or in combination with transmission images (P = 0.02), compared with the analysis of transmission radiographs only. CONCLUSIONS: The significant improvement in contrast ratios between lung parenchyma and free air in the dark-field images allows the facilitated detection of pneumothoraces in the newborn mouse. These preclinical experiments indicate the potential of the technique for future clinical applications.
AU  - Hellbach, K.*
AU  - Yaroshenko, A.*
AU  - Willer, K.*
AU  - Pritzke, T.
AU  - Baumann, A.*
AU  - Hesse, N.*
AU  - Auweter, S.*
AU  - Reiser, M.F.*
AU  - Eickelberg, O.
AU  - Pfeiffer, F.*
AU  - Hilgendorff, A.*
AU  - Meinel, F.G.*
C1  - 49386
C2  - 41811
CY  - Philadelphia
SP  - 597-601
TI  - Facilitated diagnosis of pneumothoraces in newborn mice using x-ray dark-field radiography.
JO  - Invest. Radiol.
VL  - 51
IS  - 10
PB  - Lippincott Williams & Wilkins
PY  - 2016
SN  - 0020-9996
ER  - 

TY  - JOUR
AB  - OBJECTIVES: The aim of this study was to evaluate the suitability of in vivo x-ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in mice. Furthermore, we aimed to analyze how the dark-field signal correlates with morphological changes of lung architecture at distinct stages of emphysema. MATERIALS AND METHODS: Female 8- to 10-week-old C57Bl/6N mice were used throughout all experiments. Pulmonary emphysema was induced by orotracheal injection of porcine pancreatic elastase (80-U/kg body weight) (n = 30). Control mice (n = 11) received orotracheal injection of phosphate-buffered saline. To monitor the temporal patterns of emphysema development over time, the mice were imaged 7, 14, or 21 days after the application of elastase or phosphate-buffered saline. X-ray transmission and dark-field images were acquired with a prototype grating-based small-animal scanner. In vivo pulmonary function tests were performed before killing the animals. In addition, lungs were obtained for detailed histopathological analysis, including mean cord length (MCL) quantification as a parameter for the assessment of emphysema. Three blinded readers, all of them experienced radiologists and familiar with dark-field imaging, were asked to grade the severity of emphysema for both dark-field and transmission images. RESULTS: Histopathology and MCL quantification confirmed the introduction of different stages of emphysema, which could be clearly visualized and differentiated on the dark-field radiograms, whereas early stages were not detected on transmission images. The correlation between MCL and dark-field signal intensities (r = 0.85) was significantly higher than the correlation between MCL and transmission signal intensities (r = 0.37). The readers' visual ratings for dark-field images correlated significantly better with MCL (r = 0.85) than visual ratings for transmission images (r = 0.36). Interreader agreement and the diagnostic accuracy of both quantitative and visual assessment were significantly higher for dark-field imaging than those for conventional transmission images. CONCLUSIONS: X-ray dark-field radiography can reliably visualize different stages of emphysema in vivo and demonstrates significantly higher diagnostic accuracy for early stages of emphysema than conventional attenuation-based radiography.
AU  - Hellbach, K.*
AU  - Yaroshenko, A.*
AU  - Meinel, F.G.*
AU  - Yildirim, A.Ö.
AU  - Conlon, T.M.
AU  - Bech, M.*
AU  - Mueller, M.*
AU  - Velroyen, A.*
AU  - Notohamiprodjo, M.*
AU  - Bamberg, F.*
AU  - Auweter, S.*
AU  - Reiser, M.*
AU  - Eickelberg, O.
AU  - Pfeiffer, F.*
C1  - 43789
C2  - 36767
CY  - Philadelphia
SP  - 430-435
TI  - In vivo dark-field radiography for early diagnosis and staging of pulmonary emphysema.
JO  - Invest. Radiol.
VL  - 50
IS  - 7
PB  - Lippincott Williams & Wilkins
PY  - 2015
SN  - 0020-9996
ER  - 

TY  - JOUR
AB  - OBJECTIVES: The purpose of this study was to assess whether the recently developed method of grating-based x-ray dark-field radiography can improve the diagnosis of pulmonary emphysema in vivo. MATERIALS AND METHODS: Pulmonary emphysema was induced in female C57BL/6N mice using endotracheal instillation of porcine pancreatic elastase and confirmed by in vivo pulmonary function tests, histopathology, and quantitative morphometry. The mice were anesthetized but breathing freely during imaging. Experiments were performed using a prototype small-animal x-ray dark-field scanner that was operated at 35 kilovolt (peak) with an exposure time of 5 seconds for each of the 10 grating steps. Images were compared visually. For quantitative comparison of signal characteristics, regions of interest were placed in the upper, middle, and lower zones of each lung. Receiver-operating-characteristic statistics were performed to compare the effectiveness of transmission and dark-field signal intensities and the combined parameter "normalized scatter" to differentiate between healthy and emphysematous lungs. RESULTS: A clear visual difference between healthy and emphysematous mice was found for the dark-field images. Quantitative measurements of x-ray dark-field signal and normalized scatter were significantly different between the mice with pulmonary emphysema and the control mice and showed good agreement with pulmonary function tests and quantitative histology. The normalized scatter showed a significantly higher discriminatory power (area under the receiver-operating-characteristic curve [AUC], 0.99) than dark-field (AUC, 0.90; P = 0.01) or transmission signal (AUC, 0.69; P < 0.001) alone did, allowing for an excellent discrimination of healthy and emphysematous lung regions. CONCLUSIONS: In a murine model, x-ray dark-field radiography is technically feasible in vivo and represents a substantial improvement over conventional transmission-based x-ray imaging for the diagnosis of pulmonary emphysema.
AU  - Meinel, F.G.
AU  - Yaroshenko, A.*
AU  - Hellbach, K.*
AU  - Bech, M.*
AU  - Müller, M.*
AU  - Velroyen, A.*
AU  - Bamberg, F.*
AU  - Eickelberg, O.
AU  - Nikolaou, K.*
AU  - Reiser, M.F.*
AU  - Pfeiffer, F.*
AU  - Yildirim, A.Ö.
C1  - 31376
C2  - 34445
SP  - 653-658
TI  - Improved diagnosis of pulmonary emphysema using in vivo dark-field radiography.
JO  - Invest. Radiol.
VL  - 49
IS  - 10
PY  - 2014
SN  - 0020-9996
ER  - 

TY  - JOUR
AB  - Objectives: The aim of this study was to analyze the influence of the tube current-time product in multidetector computed tomography angiography on the accuracy of stenosis quantification in a phantom model of occlusive vessel disease. Materials and Methods: Stenosed pelvic and visceral arteries were simulated using acrylic tubes (inner diameter: small, 4.0 mm; large, 6.5 mm) filled with plaque material (epoxy resin, hydroxylapatite, glass bubbles) to create different degrees of stenosis and plaque composition (calcified plaques, > 1000 Hounsfield units [HU]; soft plaques, similar to 50 HU; inhomogeneous plaques, 50-1000 HU). The lumen was filled with water-diluted contrast material (Iomeprol 400; Bracco Imaging, Konstanz, Germany) to increase the density to 350 HU. The vessel phantoms were inserted in an Alderson phantom and imaging was conducted on a 64-slice MDCT (Somatom Definition, Siemens, Forchheim, Germany; collimation, 0.6 mm; reconstructed slice thickness, 1 mm; 120 kVp) using 8 different image acquisition protocols (IAPs), with reference tube current-time products (I-QualRef) ranging between 20 and 280 mAs (IAP(20)-IAP(280)). The signal-to-noise ratio was calculated for each IAP. The measured luminal area within a stenosis was correlated to the known value using the Kappa-Lin test (kappa(Lin)). A decrease of 10% of the maximum achievable correlation was defined as substantial. The sensitivity and specificity of hemodynamically relevant stenoses (>50%) were computed. For all IAPs, the effective dose was measured with thermoluminescence dosimetry and calculated with CTEXPO 2.0 (ICRP103). Results: The measured effective dose ranged from 0.8 to 10.7 mSv. The calculated effective dose was approximately 10% lower for each IAP (0.7-9.8 mSv). A total of 2592 stenosis measurements were performed. In large vessels, the correlation was almost perfect for IAP(80) to IAP(280) (kappa(Lin) = 0.91-0.95). In comparison, overall correlation was inferior in small vessels and was substantial for IAP(280) to IAP(120) (kappa(Lin) = 0.89-0.82). Overall, the best correlation was observed in calcified (kappa(Lin) = 0.95) and soft (kappa(Lin) = 0.93) plaques as compared with inhomogeneous (kappa(Lin) = 0.89) plaques. A substantial decrease in the correlation was observed below IAP(100) for the large vessel phantoms and IAP(120) for the small vessel phantoms. The sensitivity of hemodynamically relevant stenoses was 90% to 99% for IAP(20) to IAP(280) and both vessel diameters, whereas the specificity decreased from 91% (IAP(280)) to 31% (IAP(20)) for the large vessel phantoms and from 81% to 25%, respectively, for the smaller vessel phantoms. Conclusion: In large (> 96.5 mm) vessel phantoms that simulate pelvic and renal arteries, representing a high-contrast scenario, a substantial dose reduction is feasible as compared with established abdominal imaging protocols. In smaller vessel phantoms that represent intestinal arteries, the quality of luminal delineation is already limited because of the spatial resolution. Therefore, an increase in image noise can only be accepted to a smaller degree and the potential dose reduction is limited but still substantial.
AU  - Werncke, T.*
AU  - von Falck, C.*
AU  - Taupitz, M.*
AU  - Hoeschen, C.
AU  - Wacker, F.*
AU  - Meyer, B.C.*
C1  - 8487
C2  - 30173
SP  - 530-537
TI  - Dose-wise scanning in visceral computed tomography angiography: A phantom study.
JO  - Invest. Radiol.
VL  - 47
IS  - 9
PB  - Lippincott Williams & Wilkins
PY  - 2012
SN  - 0020-9996
ER  - 

TY  - JOUR
AB  - The primary objective was to evaluate the prevalence of atherosclerotic disease, myocardial infarctions, and cerebrovascular disease in patients with long-standing diabetes using whole-body magnetic resonance imaging (WB-MRI) combined with whole-body magnetic resonance angiography (WB-MRA) and to estimate the cumulative disease burden in a new MRA-based score. Materials and Methods: The study was approved by the ethics committee and all patients gave informed written consent. Sixty-five patients with long-standing (>10 years) diabetes mellitus without acute symptoms were prospectively evaluated. The patients were clinically assessed and received WB-MRI/WB-MRA containing an examination of the brain, the heart, the arterial vessels (abdominal aorta, the supraaortic, renal, pelvic, and peripheral arteries), and the feet. Prevalence rates were calculated and compared with a healthy control group of 200 individuals after adjustment for age and sex by a logistic regression analysis using exact parameter estimates (Cochran-Mantel-Haenszel-statistics). Finally, an MRA based vessel score (sum of grades of all evaluated vessels divided by the number of vessels; grades range from 1, normal, to 6, complete occlusion) indicative of atherosclerotic disease burden was created for this study. This vessel score's association with clinical and biochemical parameters (age, sex, type of diabetes, diabetes duration, body mass index, blood pressure, smoking, coronary artery disease-status, retinopathy, serum creatinine, hemoglobin A1c test, low density lipoprotein- concentration, medication) was assessed with an age and sex adjusted analysis (generalized linear model). Results: In the diabetic patients, we found prevalence rates of 49% for peripheral artery disease, 25% for myocardial infarction, 28% for cerebrovascular disease, and 22% for neuropathic foot disease. In all vascular beds, at least 50% of the pathologies were previously unknown. Myocardial infarction (P = 0.0002), chronic ischemic cerebral lesions (P = 0.0008), and atherosclerotic disease were significantly more common in diabetic than in control subjects (internal carotid artery: P = 0.006, vertebral artery: P = 0.009, intracerebral vessels: P = 0.02, superficial femoral artery: P = 0.006, anterior tibial artery: P = 0.01, posterior tibial artery: P = 0.02, fibular artery: 0.003). The WB-MRI/WB-MRA-based score showed a significant association with age (P = 0.0008), male sex (P = 0.03), nephropathy (P = 0.006), diabetic retinopathy (P = 0.007), and coronary artery disease status (P = 0.006). Body mass index, blood pressure, hemoglobin A1c test, low density lipoprotein-cholesterol, and medications showed no significant association with the score. Conclusions: Using WB-MRI combined with WB-MRA we found a high prevalence of occult atherosclerotic disease in long-standing diabetic patients. This study shows that the true atherosclerotic burden in these patients is largely underestimated.
AU  - Weckbach, S.*
AU  - Findeisen, H.M.*
AU  - Schoenberg, S.O.*
AU  - Kramer, H.*
AU  - Stark, R.G.
AU  - Clevert, D.A.*
AU  - Reiser, M.F.*
AU  - Parhofer, K.G.*
C1  - 1011
C2  - 26426
SP  - 242-250
TI  - Systemic cardiovascular complications in patients with long-standing diabetes mellitus: Comprehensive assessment with whole-body magnetic resonance imaging/magnetic resonance angiography.
JO  - Invest. Radiol.
VL  - 44
IS  - 4
PB  - Lippincott Williams & Wilkins
PY  - 2009
SN  - 0020-9996
ER  - 

TY  - JOUR
AB  - Objectives: Thermal dose in tumor tissue is a key factor for regional hyperthermia (HT) combined with chemotherapy and for drug delivery using thermosensitive liposomes (TSL). It influences therapy outcome. affects the accumulation of liposomes, and triggers the content release from TSL in the target tissue. For the development and clinical application of TSL, noninvasive visualization is of critical importance. For this purpose, TSL loaded with MRI contrast agent (ICA) have been developed. With increase in temperature, the CA is released from TSL at the phase transition temperature T-m resulting in a relaxation time change, which allows MRI monitoring. The purpose of this study was to examine the feasibility of an in vivo application and MR characterization of Gd-DTPA-BMA-loaded phosphatidylglyceroglycerol-TSL (Gd-TSL) at mild HT conditions in tumor tissue using a clinically relevant setting. Material and Methods: Gd-TSL were characterized in vitro with varying thermal doses between 37 degrees C and 45 degrees C and distinct solvents by MR at 0.5 T and 1.5 T. In vivo Studies were performed in C57BL/6 mice bearing BFS-1 fibrosarcomas at 1.5 T. One tumor-bearing leg was immersed in it temperature-control led water bath (T). Gd-TSL (T-m = 43.5 +/- 0.2 degrees C) were injected either intratumorally or intravenously at T = 37.3 +/- 0.1 degrees C or T = 42.5 +/- 0.3 degrees C. As a control, nonliposomal Gd-DTPA-BMA was injected intravenously at T = 43.1 +/- 0.3 degrees C. A second tumor on the contralateral limb, which remained unheated. served as a control. CA release was monitored by T-1-weighted spin-echo. Results: The in vitro characterization demonstrated at heated and unheated samples a strong increase in T-1-relaxivity of Gd-TSL solutions from 0.4 mM(-1) s(-1) (37.5 degrees C) to 4.2 mM(-1) s(-1) (43.3 degrees C) at 0.5 T. Thermal dose and solvent affected the rate of relaxation time change significantly. A fast and complete release was observed in samples with serum, whereas Gd-TSL in glucose was only partially released within 1 hour. A dedicated experimental setup was developed for standardized in vivo investigation. Tumor signal intensity changes were detectable in all animals. After intratumoral injection of Gd-TSL, the signal increased heterogeneously (max., +52% +/- 25%) within 3 minutes after temperature increase and decreased strongly thereafter, whereas after i.v. injection, the signal increased homogeneously (+ 19% +/- 3%) within 2 minutes persisting thereafter. The unheated control tumors on the contralateral legs showed a 10% +/- 3% signal increase within 2 minutes. Injection at 37 degrees C showed a continuous signal increase in "heated" and unheated tumors of up to 8% to 10%. Nonliposomal CA injection demonstrated that tumors were well perfused during HT. Conclusion: HT-induced CA release from Gd-TSL was monitored and characterized by MRI after i.v. injection in tumor-bearing mice. Higher temperatures resulted in higher signal changes. Immediately after i.v. injection, heated tumor tissue was distinguishable from unheated tumor tissue. The Gd-TSL appears to be suitable for MR monitoring of HT tumor treatment in a clinical MRI setting independent of field strength.
AU  - Peller, M.*
AU  - Schwerdt, A.*
AU  - Hossann, M.*
AU  - Reinl, H. M.*
AU  - Wang, T.
AU  - Sourbron, S.*
AU  - Ogris, M.*
AU  - Lindner, L.H.
C1  - 3335
C2  - 25838
SP  - 877-892
TI  - MR characterization of mild hyperthermia-induced gadodiamide release from thermosensitive liposomes in solid tumors.
JO  - Invest. Radiol.
VL  - 43
IS  - 12
PB  - Lippincott Williams & Wilkins
PY  - 2008
SN  - 0020-9996
ER  -