EFSUMB Technical Review - Update 2023: Dynamic Contrast-Enhanced Ultrasound (DCE-CEUS) for the Quantification of Tumor Perfusion.

Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.

Dynamic contrast-enhanced ultrasound and elastography assess deltoid muscle integrity after reverse shoulder arthroplasty.

BACKGROUND: The outcome after reverse shoulder arthroplasty (RSA) depends on the condition of the deltoid muscle, which we assessed with new ultrasound modalities and electromyography (EMG). Contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) were applied to assess perfusion and elasticity of the deltoid muscle compared with the clinical and functional outcome. METHODS: The study recruited 64 patients (mean age, 72.9 years) treated with RSA between 2004 and 2013. The deltoid muscle was examined with EMG and ultrasound imaging. Functional scores such as Constant score and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score were assessed. Among other CEUS parameters, the wash-in perfusion index, time to peak, and rise time were compared between the operated-on and contralateral shoulders as well as between patients with above-average and below-average outcome. The stiffness of the deltoid muscle was analyzed with ARFI. RESULTS: After RSA, deltoid perfusion (wash-in perfusion index, Δ = -12% ± 22%, P = .0001) and shoulder function (Constant score, Δ = -14 ± 24, P < .0001) were both inferior compared with the contralateral side. This perfusion deficit was associated with a limited range of motion (time to peak and anteversion: r = -0.290, P = .022). Deltoid perfusion was higher in patients with above-average outcome (rise time, Δ = 33% ± 13%, P = .038). The operated-on deltoid muscles showed higher stiffness than the contralateral muscles (ARFI, Δ = 0.2 ± 0.9 m/s, P = .0545). EMG excluded functionally relevant axillary nerve injuries in the study population. CONCLUSIONS: CEUS revealed reduced mean perfusion of the deltoid muscle after RSA. Reduced perfusion was associated with limited range of motion and below-average outcome. Functional shoulder impairment after RSA might be predicted by noninvasive CEUS as a surrogate parameter for the integrity of the deltoid muscle.

Dynamic Contrast-Enhanced Sonography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Preoperative Diagnosis of Infected Nonunions.

OBJECTIVES: Bone regeneration depends on perfusion of the fracture tissue, whereby hypervascularity is associated with infection, which itself causes nonunions. To date, nonunion perfusion has not been assessed with contrast-enhanced sonography. The aim of this study was to evaluate the potential of contrast-enhanced sonography in the analysis of nonunion tissue perfusion. METHODS: Nonunion vascularity of 31 patients before revision surgery was prospectively examined with qualitative contrast-enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging (MRI). Time-intensity curves from 2-minute contrast-enhanced sonographic video clips were generated, and parameters such as wash-in rate, rise time, and peak enhancement were quantified. On dynamic contrast-enhanced MRI, the initial area under the enhancement curve was quantified. Preoperative radiographs, computed tomograms, the clinical nonunion score, laboratory infection features, as well as contrast-enhanced sonographic and dynamic contrast-enhanced MRI perfusion were correlated with microbiological results from the nonunion tissue. RESULTS: Both qualitative and quantitative contrast-enhanced sonography showed significant differences between infected and aseptic nonunions (P = .015 and .020). The qualitative dynamic contrast-enhanced MRI analysis was not significant (P= .244), but after quantification, a strong correlation (P = .007) with microbiological results was noted. A receiver operating characteristic analysis calculated ideal cutoff values for quantitative contrast-enhanced sonography and dynamic contrast-enhanced MRI so that their combination detected infected nonunions with sensitivity and specificity of 88.9% and 77.3%, respectively. Clinical, radiologic, and laboratory examinations did not correlate with microbiological results (P > .05). CONCLUSIONS: Contrast-enhanced sonography can visualize the vascularity of nonunions in real time, while quantification software allows for a semiobjective evaluation of bone perfusion. The correlations of both quantitative contrast-enhanced sonography and dynamic contrast-enhanced MRI with microbiological results show their high value for differentiation of infected from aseptic nonunions.

High-contrast computed tomographic angiography better detects residual intracranial arteriovenous malformations in long-term follow-up after radiotherapy than 1.5-Tesla time-of-flight magnetic resonance angiography.

BACKGROUND: Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are noninvasive alternatives for therapy monitoring of cerebral arteriovenous malformation (AVM). PURPOSE: To evaluate if CTA is able to detect residual AVM in the long-term follow-up after radiotherapy when time-of-flight (TOF) MRA could no longer detect a remaining nidus. MATERIAL AND METHODS: 18 patients with intracranial AVM were included between November 2005 and August 2007 who were scheduled for CTA (16-slice CT, 1-mm slice thickness, 90 ml iomeprol 400 mg I/ml, 4 ml/s) in the follow-up of radiotherapy. In these patients, MRA (3D-TOF, and bolus tagging at 1.5 T) could no longer detect a remaining nidus. RESULTS: The previously performed MRA (median time between CTA and MRA, 2.5 months) described total obliterations in 14 and subtotal obliterations in two AVM cases. Two MRA diagnoses were inconclusive due to artifacts. CTA (median time after therapy, 28 months; range, 5-66 months) could provide a diagnosis in all cases, but confirmed the MRA diagnosis only in 50% of the cases. A residual nidus was shown in an additional six cases, and subtotal obliteration in another three cases. The interval between radiotherapy and the follow-up examination was significantly different (P<0.05) between false- and true-negative MRA examinations (median, 18 vs. 30 months). CONCLUSION: High-contrast CTA is a sensitive tool in the detection of AVM and is able to identify residual AVM after radiotherapy even if previously performed TOF MRA at 1.5 T shows total obliteration.

Contrast-Enhanced Ultrasound for Musculoskeletal Applications: A World Federation for Ultrasound in Medicine and Biology Position Paper.

This World Federation for Ultrasound in Medicine and Biology position paper reviews the diagnostic potential of ultrasound contrast agents for clinical decision-making and provides general advice for optimal contrast-enhanced ultrasound performance in musculoskeletal issues. In this domain, contrast-enhanced ultrasound performance has increasingly been investigated with promising results, but still lacks everyday clinical application and standardized techniques; therefore, experts summarized current knowledge according to published evidence and best personal experience. The goal was to intensify and standardize the use and administration of ultrasound contrast agents to facilitate correct diagnoses and ultimately to improve the management and outcomes of patients.

Morphology, metabolism, microcirculation, and strength of skeletal muscles in cancer-related cachexia.

PURPOSE: Cancer-related cachexia is an obscure syndrome leading to muscle wasting, reduced physical fitness and quality of life. The aim of this study was to assess morphology, metabolism, and microcirculation in skeletal muscles of patients with cancer-related cachexia and to compare these data with matched healthy volunteers. METHODS: In 19 patients with cancer-induced cachexia and 19 age-, gender-, and body-height-matched healthy volunteers body composition and aerobic capacity (VO(2max)) were analyzed. Skeletal muscle fiber size and capillarization were evaluated in biopsies of the vastus lateralis muscle. The cross-sectional area (CSA) of the quadriceps femoris muscle was measured by magnetic resonance imaging as well as its isokinetic and isometric force. The energy and lipid metabolism of the vastus lateralis muscle was quantified by (31)P and (1)H spectroscopy and parameters of its microcirculation by contrast-enhanced ultrasonography (CEUS). RESULTS: Morphologic parameters were about 30% lower in cachexia than in volunteers (body mass index: 20 +/- 3 vs. 27 +/- 4 kg m(-2), CSA: 45 +/- 13 vs. 67 +/- 14 cm(2), total fiber size: 2854 +/- 1112 vs. 4181 +/- 1461 microm(2)). VO(2max) was reduced in cachexia (23 +/- 9 vs. 32 +/- 7 ml min(-1) kg(-1), p=0.03), whereas histologically determined capillary density and microcirculation in vivo were not different. Both concentrations of muscular energy metabolites, pH, and trimethyl-ammonium-containing compounds were comparable in both groups. Absolute strength of quadriceps muscle was reduced in cachexia (isometric: 107 +/- 40 vs. 160 +/- 40 Nm, isokinetic: 101 +/- 46 vs. 167 +/- 50 Nm; p=0.03), but identical when normalized on CSA (isometric: 2.4 +/- 0.5 vs. 2.4 +/- 0.4 Nm cm(-2), isokinetic: 2.2 +/- 0.4 vs. 2.5 +/- 0.5 Nm cm(-2)). CONCLUSIONS: Cancer-related cachexia is associated with a loss of muscle volume but not of functionality, which can be a rationale for muscle training.

Assessment of metabolism and microcirculation of healthy skeletal muscles by magnetic resonance and ultrasound techniques.

PURPOSE: To assess metabolism and microcirculation of healthy skeletal muscle by magnetic resonance (MR) and ultrasound techniques and to compare these data with muscle histology, and anthropometric and blood parameters. METHODS: Thirty-four healthy volunteers were selected such that their measured aerobic capacity (VO2max) per body weight ranged between 23 and 66 mL/minute/kg to render a large variability of skeletal muscle capillarization as a result of their different physical activity. We analyzed body composition, blood parameters, and skeletal muscle fiber size and capillarization in biopsies of the vastus lateralis muscle. These data were compared with knee extensor cross-sectional area (CSA) obtained by MR imaging, microcirculation of the vastus lateralis muscle by contrast-enhanced ultrasound (CEUS), and its energy and lipid metabolism measured with 31P and 1H MR spectroscopy. Statistical analysis was performed using Pearson's correlation coefficient and significance was tested at a level of .5%. RESULTS: The variable physical activity was reflected in a large variability of vastus lateralis muscle perfusion and metabolism at rest with highest histologic capillarization and CEUS-perfusion values observed in the best-trained volunteers. Levels of high-energy phosphates, such as phosphocreatine, were positively correlated with CSA (r= .5) and histologic fiber size (r= .6 for type IIA and IIX fibers), while phosphocreatine concentration was significantly negatively correlated to myocellular lipids (r=-.6) and trimethyl ammonium containing compounds (r=-.8). Local blood volume measured in vivo with CEUS was positively correlated with several histologic capillarization parameters. CONCLUSIONS: Dedicated MR- and CEUS-methods deliver (patho-)physiologic information about capillarization and fiber characteristics of skeletal muscles in vivo and hence establish a useful diagnostic tool for muscular diseases.

Low radiation dose in computed tomography: the role of iodine.

Recent approaches to reducing radiation exposure during CT examinations typically utilize automated dose modulation strategies on the basis of lower tube voltage combined with iterative reconstruction and other dose-saving techniques. Less clearly appreciated is the potentially substantial role that iodinated contrast media (CM) can play in low-radiation-dose CT examinations. Herein we discuss the role of iodinated CM in low-radiation-dose examinations and describe approaches for the optimization of CM administration protocols to further reduce radiation dose and/or CM dose while maintaining image quality for accurate diagnosis. Similar to the higher iodine attenuation obtained at low-tube-voltage settings, high-iodine-signal protocols may permit radiation dose reduction by permitting a lowering of mAs while maintaining the signal-to-noise ratio. This is particularly feasible in first pass examinations where high iodine signal can be achieved by injecting iodine more rapidly. The combination of low kV and IR can also be used to reduce the iodine dose. Here, in optimum contrast injection protocols, the volume of CM administered rather than the iodine concentration should be reduced, since with high-iodine-concentration CM further reductions of iodine dose are achievable for modern first pass examinations. Moreover, higher concentrations of CM more readily allow reductions of both flow rate and volume, thereby improving the tolerability of contrast administration.

Contrast-enhanced ultrasound in dermatomyositis- and polymyositis.

OBJECTIVE: To evaluate prospectively contrast-enhanced ultrasound (CEUS) in patients suspected of having dermatomyositis or polymyositis. METHODS: In 35 patients (23 women, 12 men; mean age, 51 years+/-16 years) who were suspected of having dermatomyositis or polymyositis, perfusion in clinically affected skeletal muscles was quantified with contrast-enhanced intermittent power Doppler ultrasound. By applying a modified model that analyzed the replenishment kinetics of microbubbles, the perfusion-related parameters blood flow, local blood volume and blood flow velocity were measured. Findings were compared with muscle biopsy appearances and with the results of MRI that was performed with a 1.5-Tesla unit. Receiver operating characteristic analysis was performed and optimum thresholds for diagnosis of myositis were determined. RESULTS: Eleven patients had histologically confirmed dermatomyositis or polymyositis and showed significantly higher blood flow velocity (P=.01 for dermato- and P<.001 for polymyositis), blood flow (P<.001 for dermato- and polymyositis), and blood volume (P=.007 for dermato- and P<.001 for polymyositis) on contrast-enhanced ultrasound than those who did not have myositis. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis. MRI had a sensitivity, specificity, positive (PPV), and negative predicting values (NPV) of 100%, 88%, 77%, and 100% for diagnosis of myositis, respectively. CEUS blood flow was the best ultrasound measure for diagnosis of dermato- or polymyositis with sensitivity, specificity, PPV, and NPV of 73%, 91%, 80%, and 88%, respectively. CONCLUSIONS: Increased skeletal muscle perfusion measured by CEUS could serve as an additional measurer for the diagnosis of an inflammatory myopathy.

Sensitive noninvasive monitoring of tumor perfusion during antiangiogenic therapy by intermittent bolus-contrast power Doppler sonography.

Intermittent bolus-contrast power Doppler ultrasound was used for noninvasive, quantitative monitoring of tumor perfusion during antiangiogenic therapy. Subcutaneous heterotransplants of human squamous cell carcinoma cells in nude mice were treated with a blocking antibody to vascular endothelial growth factor receptor 2 (DC101) and repeatedly examined at weekly intervals. Using replenishment kinetics of microbubbles (Levovist) tumor vascularization, including capillary blood flow, was clearly visualized by this dynamic ultrasound method allowing the determination of a comprehensive functional status of tumor vascularization (blood volume, blood flow, perfusion, and mean blood velocity) in all examined tumors. DC101 treatment decreased tumor blood flow (-64%) and volume (-73%) compared with untreated controls (+409% and +185%, respectively). Regression of functional vessel parameters was observed early well before reduction of tumor size. The treatment-related amount of reduction in tumor volume was directly correlated for the initial tumor blood flow before start of therapy and the perfusion calculated at the preceding examination. The vessel density (immunofluorescence staining with CD31 antibody at different time points) showed an excellent correlation with the calculated relative blood volume (k = 0.84, P < 0.01), thereby validating intermittent sonography as a useful monitoring method. We conclude that intermittent sonography is a promising tool for comprehensive monitoring of antiangiogenic or proangiogenic therapies, especially during early stages of treatment, thus yielding information regarding a prospective evaluation of therapy effects beyond the follow up of tumor size.

Combined therapy with direct and indirect angiogenesis inhibition results in enhanced antiangiogenic and antitumor effects.

The multifaceted nature of the angiogenic process in malignant neoplasms suggests that protocols that combine antiangiogenic agents may be more effective than single-agent therapies. However it is unclear which combination of agents would be most efficacious and will have the highest degree of synergistic activity while maintaining low overall toxicity. Here we investigate the concept of combining a "direct" angiogenesis inhibitor (endostatin) with an "indirect" antiangiogenic compound [SU5416, a vascular endothelial growth factor receptor 2 (VEGFR2) receptor tyrosine kinase (RTK) inhibitor]. These angiogenic agents were more effective in combination than when used alone in vitro (endothelial cell proliferation, survival, migration/invasion, and tube formation tests) and in vivo. The combination of SU5416 and low-dose endostatin further reduced tumor growth versus monotherapy in human prostate (PC3), lung (A459), and glioma (U87) xenograft models, and reduced functional microvessel density, tumor microcirculation, and blood perfusion as detected by intravital microscopy and contrast-enhanced Doppler ultrasound. One plausible explanation for the efficacious combination could be that, whereas SU5416 specifically inhibits vascular endothelial growth factor signaling, low-dose endostatin is able to inhibit a broader spectrum of diverse angiogenic pathways directly in the endothelium. The direct antiangiogenic agent might be able to suppress alternative angiogenic pathways up-regulated by the tumor in response to the indirect, specific pathway inhibition. For future clinical evaluation of the concept, a variety of agents with similar mechanistic properties could be tested.

Dynamic contrast-enhanced magnetic resonance imaging rapidly indicates vessel regression in human squamous cell carcinomas grown in nude mice caused by VEGF receptor 2 blockade with DC101.

The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31). Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02). In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/- 843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/- 93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.

Dynamic magnetic resonance tomography and proton magnetic resonance spectroscopy of prostate cancers in rats treated by radiotherapy.

RATIONALE AND OBJECTIVES: To establish an experimental setting for monitoring perfusion and metabolism in orthotopic prostate cancer at 1.5 T using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and 1H-MR spectroscopy (MRS). METHODS: Dunning rat prostate cancer cells were injected into the prostate by open surgery. Twelve tumor-bearing rats (5 of these irradiated) and 6 healthy controls were followed up using gadolinium-diethylenetriaminepentaacetic acid -enhanced dynamic MRI and 1H-MRS. Amplitude and the exchange rate constant kep were calculated (2-compartment model). From 1H-MR spectra, ratios of choline (Cho) and creatine (tCr) were calculated. All tumors were examined histologically. RESULTS: On DCE MRI parameter maps, tumors showed increased vascularization. kep and microvessel density were correlated (r = 0.97). Tumors showed elevated Cho/tCr and an unexpected lipid fraction (2.0-2.2 parts per million). Irradiation slowed tumor growth significantly. Changes of perfusion and metabolism could be detected in all tumors during follow up. CONCLUSION: DCE MRI and 1H-MRS has potential to characterize orthotopic Dunning prostate cancer in rats, which is a promising model similar to human prostate carcinomas.

Low mechanical index contrast-enhanced ultrasound better reflects high arterial perfusion of liver metastases than arterial phase computed tomography.

RATIONALE AND OBJECTIVES: We investigated whether observing the arterial vascularization of liver metastases by contrast-enhanced ultrasound with low mechanical index (low-MI) imaging offers additional diagnostic information for the characterization of the liver lesions. METHODS: Twenty nine patients with untreated liver metastases of different primaries were examined. Measurements were performed using a low frame rate, low-MI pulse inversion technique after injection of 2.4 mL SonoVue. The relative maximum signal intensity of the liver lesions related to the normal liver tissue was quantified. Ultrasound findings were compared with contrast-enhanced, dual-phase computed tomography (CT) using a pattern-based classification scheme. RESULTS: Compared with contrast-enhanced CT, this modality better detects arterial perfusion. Metastases, even those usually considered hypovascularized, often showed homogeneous enhancement (66%) and higher arterial vascularization than normal liver tissue. CT did not show a comparable vascularization pattern (P < 0.001) or any similarly early signal intensity (P < 0.001). CONCLUSIONS: Contrast-enhanced CT may not be able to visualize short-lasting but large differences of the arterial perfusion of liver metastases, as does contrast-enhanced low-MI ultrasound. This offers new methods for their characterization and for monitoring of therapeutic effects.

Comparing dynamic parameters of tumor vascularization in nude mice revealed by magnetic resonance imaging and contrast-enhanced intermittent power Doppler sonography.

RATIONALE: Angiogenesis is essential for spread and growth of malignant tumors. Because noninvasive methods for observing tumor vascularization are limited, most of previous results were based on histologic findings alone. In this study, dynamic parameters obtained using intermittent contrast-enhanced Doppler sonography and dynamic MRI were compared and correlated with microvessel density. METHODS: Eleven tumor-bearing nude mice were examined with dynamic T(1)-weighted sequences using Gd-DTPA in a 1.5 T magnetic resonance (MR) scanner and with intermittent power Doppler sonography after a single bolus of galactose based contrast agent. After examination 6 tumors were harvested for immunofluorescence microscopy using a CD31 stain. Using a 2-compartment model, the MR parameters amplitude (reflecting plasma volume) and k(ep) (influenced by the vessel permeability) were calculated and compared with maximal enhancement (max) and perfusion P measured with ultrasound. RESULTS: The MR amplitude correlated with the ultrasound parameter max significantly (r = 0.61; P = 0.01). Max (r = 0.67; P = 0.01), amplitude (r = 0.72; P = 0.01), and perfusion (r = 0.62; P = 0.05) correlated with the microvessel density. k(ep) moderately correlated with max, but not with perfusion and microvessel density. CONCLUSIONS: Dynamic MRI and contrast enhanced ultrasound are supplementing methods for examining perfusion and vascularity of experimental tumors.

A multivessel model describing replenishment kinetics of ultrasound contrast agent for quantification of tissue perfusion.

To improve the quantification of tissue perfusion using intermittent sonography, a new model describing replenishment kinetics of microbubbles is proposed. The new approach takes into account the variability of blood flow velocities found in vivo, especially in tumors, and consistently describes the refilling process of microbubbles. Based upon this model, blood volume, blood velocity, blood flow and perfusion in 17 experimental tumors were calculated, and compared with the results obtained with the established, phenomenologically derived exponential kinetic model. In contrast to the existing model, our approach describes tissue vascularization more physiologically and allows deduction of a consistent new hyperbolic model for quantification of intermittent sonography. Blood volume and mean blood velocity did significantly correlate between both the new and the established model (k=0.99; k=0.94, both p<0.001). However, mean tumor blood velocity was lower (-19%, p<0.01) with the established model compared to the newly developed model. In addition, the range and distribution of blood flow velocities found in vivo can be estimated with the new model. Furthermore, it uses simpler mathematical fitting routines and allows easier data acquisition, which may allow a more practicable clinical application of intermittent sonography. In conclusion, a more valid, detailed and accurate calculation of perfusion parameters, especially of tumors, can be derived in vivo with the new multivessel model of intermittent sonography.

Comparison of intermittent-bolus contrast imaging with conventional power Doppler sonography: quantification of tumour perfusion in small animals.

Replenishment kinetics of microbubbles were adapted to a single bolus injection to investigate tumour angiogenesis in small animals with intermittent imaging, and to compare vascularisation parameters from this new approach with conventional power Doppler ultrasound (US). A reformulation of the imaging protocol and the derivation of perfusion parameters was necessary, taking into account the time-dependence of the systemic microbubble concentration after single bolus injection. Using this new method, tumour vascularisation was evaluated in 13 experimental murine tumours. Furthermore, parameters calculated with intermittent imaging after bolus injection of 100 microl Levovist were compared with parameters from the signal intensity-time curve. The results showed that quantifying tumour perfusion, blood volume and flow, as well as the assessment of the mean blood velocity (in m/s), is possible in tumours with a volume of more than 0.1 mL. In larger tumours, a lower perfusion was calculated than in smaller ones (k = -0.88; p < 0.001). Only limited correlations were found between conventional power Doppler US quantities and parameters of intermittent sonography: Perfusion correlated with the maximum signal intensity (k = 0.61, p < 0.05) and the gradient to maximum (k = 0.82, p < 0.01), full width-half maximum was associated with blood volume (k = 0.62, p < 0.05). We conclude that intermittent bolus contrast sonography allows the quantification of tumour perfusion, even in small animals, and the monitoring of basic antiangiogenic studies with perfusion parameters shows a higher significance than conventional power Doppler US.

Quantification of perfusion of liver tissue and metastases using a multivessel model for replenishment kinetics of ultrasound contrast agents.

Low-MI (mechanical index) ultrasound allows real-time observation of replenishment kinetics after destruction ("flash") of ultrasound contrast agents (USCA). We developed an examination protocol and a mathematical model to quantify perfusion of liver tissue and hepatic metastases. Using a modified multivessel model, we attempted a consistent, physiological description of microbubble replenishment in liver tissue. Perfusion parameters were calculated, separately for the arterial and portal venous phase of liver perfusion, using an i.v. bolus injection of 2 x 2.4 mL SonoVue. The model was evaluated for 10 examinations of liver metastases using flash/low-MI imaging. In contrast to the established, exponential model, the new model consistently describes the sigmoid replenishment of USCA measured in vivo, using flash/low-MI imaging. Parameters for blood volume, blood velocity and blood flow in liver tissue and metastases can be calculated during the arterial and the portal venous phase after a CA bolus injection. The median arterial perfusion in the examined liver metastases was more than 2.5 times higher than in normal liver tissue, whereas the median perfusion during the portal venous phase was more than five times higher in the liver tissue than that in metastases. Microbubble replenishment measured with flash/low-MI US techniques can be consistently analyzed using the multivessel model, even after a bolus injection of USCA. This allows for the quantification of perfusion of liver tissue and hepatic metastases and provides promising parameters of tissue viability and tumor characterization.

Evaluation of a high iodine delivery rate in combination with low tube current for dose reduction in pulmonary computed tomography angiography.

PURPOSE: The present study evaluates the combination of a high iodine delivery rate with a low tube current-time product for pulmonary computed tomography angiography (CTA). MATERIALS AND METHODS: One-hundred nineteen consecutive patients undergoing pulmonary CTA for suspected pulmonary embolism were included and imaged on a 128-row computed tomography scanner at 100 kVp using highly concentrated contrast material (85 mL Iomeprol; 400 mg iodine/mL). The protocol entailed a flow rate of 5 mL/s and 90 mAs for group A, 3.5 mL/s and 135 mAs for group B, 5 mL/s and 135 mAs for group C, and 3.5 mL/s and 90 mAs for group D. Signal-to-noise ratio and contrast-to-noise ratio (CNR) were determined for the pulmonary artery. Subjective image quality (IQ) was rated on a 5-point scale (1=nondiagnostic IQ to 5=excellent IQ). RESULTS: CNR did not differ significantly between groups A (43.7±27.7), B (34.5±17.9), and C (38.9±13.8), as well as between groups B and D (29.9±11.2). CNR was higher in groups A and C than in group D (P<0.02). Subjective IQ was higher in group A than in groups B and D (P<0.05). Subjective IQ was significantly higher in group A compared with group D (P=0.026) and in group C compared with group D (P=0.007). CONCLUSIONS: A high iodine delivery rate permits dose reduction in pulmonary CTA and can be recommended in patients with suspected pulmonary embolism.

Assessment of skeletal muscle microcirculation in type 2 diabetes mellitus using dynamic contrast-enhanced ultrasound: a pilot study.

PURPOSE: To investigate muscular micro-perfusion by employing dynamic contrast-enhanced ultrasound (CEUS) and performing transient arterial occlusion in patients with type 2 diabetes mellitus (DM-2). METHODS: Twenty DM-2 patients (mean age, 58 ± 8.6 years; duration of diabetes, 15.4 ± 12.1 years) and 20 healthy volunteers (mean age, 54 ± 5.4 years) participated. CEUS was applied to the calf, while 4.8 mL of SonoVue(®) was injected intravenously. At the thigh level, arterial occlusion (60 s) was performed. CEUS parameters (tmax, max, AUCpost and m) were evaluated and Pearson-product-moment correlation coefficients were computed. RESULTS: A moderate negative correlation of HbA1c and max was established (-0.53). Max in patients with DM-2 >10 years was 79.89 ± 37.4. Max in patients with DM-2 duration <10 years was 137.62 ± 71.72 (p = 0.04). AUCpost in patients with DM-2 duration >10 years was 3924.01 ± 1630.52. AUCpost in patients with DM-2 duration <10 years was 6453.59 ± 3206.23 (p = 0.04). CONCLUSION: Patients with long history of DM-2 present with impaired muscular perfusion. CEUS and transient arterial occlusion may provide appropriate methods for semi-quantitative evaluation of muscular micro-perfusion in patients with DM-2.