Arterial input function calculation in dynamic contrast-enhanced MRI: an in vivo validation study using co-registered contrast-enhanced ultrasound imaging.

OBJECTIVES: Developing a method of separating intravascular contrast agent concentration to measure the arterial input function (AIF) in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of tumours, and validating its performance in phantom and in vivo experiments. METHODS: A tissue-mimicking phantom was constructed to model leaky tumour vasculature and DCE-MR images of this phantom were acquired. An in vivo study was performed using tumour-bearing rabbits. Co-registered DCE-MRI and contrast-enhanced ultrasound (CEUS) images were acquired. An independent component analysis (ICA)-based method was developed to separate the intravascular component from DCE-MRI. Results were validated by comparing the time-intensity curves with the actual phantom and in vivo curves. RESULTS: Phantom study: the AIF extracted using ICA correlated well with the true intravascular curve. In vivo study: the AIFs extracted from DCE-MRI using ICA were very close to the true AIF. Intravascular component images were very similar to the CEUS images. The contrast onset times and initial wash-in slope of the ICA-derived AIF showed good agreement with the CEUS curves. CONCLUSION: ICA has the potential to separate the intravascular component from DCE-MRI. This could eliminate the requirement for contrast medium uptake measurements in a major artery and potentially result in more accurate pharmacokinetic parameters. KEY POINTS: • Tumour response to therapy can be inferred from pharmacokinetic parameters. • Arterial input function (AIF) is required for pharmacokinetic modelling of tumours. • Independent component analysis has the potential to measure AIF inside the tumour. • AIF measurement is validated using contrast enhanced ultrasound and phantoms.

Development of a platform for co-registered ultrasound and MR contrast imaging in vivo.

Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.

Demonstration of second-harmonic IVUS feasibility with focused broadband miniature transducers.

Focused broadband miniature polyvinylidene fluoride-trifluoroethylene (PVDF TrFE) ultrasonic transducers were investigated for intravascular (IVUS) second-harmonic imaging. Modeling and experimental studies demonstrated that focused transducers, unlike conventional flat transducers, build up second harmonic peak pressures faster and stronger, leading to an increased SNR of second harmonic content within the coronary geometry. Experimental results demonstrated that focused second harmonic pressures could be controlled to occur at specific depths by controlling the f-number of the transducer. The experimental results were in good agreement with the modeled results. Experiments were conducted using three imaging modalities: fundamental 20 MHz (F20), second harmonic 40 MHz (H40), and fundamental 40 MHz (F40). The lateral resolutions for a 1-mm transducer (f-number 3.2) at F20, F40, and H40 were experimentally measured to be 162, 123, and 124 microm, respectively, which agreed well with the theoretical calculations with <<8% error. Lateral resolution was further characterized in the three modes, using a micromachined phantom consisting of fixed bars and spaces with widths ranging from 20 to 160 microm. H40 exhibited better lateral resolution, clearly displaying 40- and 60-microm bars with about 4 dB and 7 dB greater signal strength compared with F20. Ex vivo human aorta images were obtained in the second-harmonic imaging mode to show the feasibility of high resolution second-harmonic IVUS using focused transducers.

Design and analysis of MEMS based PVDF ultrasonic transducers for vascular imaging.

Polyvinilidene fluoride (PVDF) single-element transducers for high-frequency (>30 MHz) ultrasound imaging applications have been developed using MEMS (Micro-electro-Mechanical Systems) compatible techniques. Performance of these transducers has been investigated by analyzing the sources and effects of on-chip parasitic capacitances on the insertion-loss of the transducers. Modeling and experimental studies showed that on-chip parasitic capacitances degraded the performance of the transducers and an improved method of fabrication was suggested and new devices were built. New devices developed with minimal parasitic effects were shown to improve the performance significantly. A 1-mm aperture PVDF device developed with minimal parasitic effects has resulted in a reduction of insertion loss of 21 dB compared with devices fabricated using a previous method.