# Contrast-Enhanced Ultrasound Imaging Based on Bubble Region Detection
## 1 Introduction  
Ultrasound contrast agents (UCAs) [1; 2] are a type of diagnostic reagents that typically consist of gas-filled microbubbles with a diameter ranging from 1 to 10 \(\upmu\)m. The microbubbles are filled with low solubility gas and are coated with a shell to prevent the microbubble from dissolving. UCAs are injected intravenously into the body and are considered safe for use in humans. UCAs have been used clinically since the 1980s [1]. Ultrasound contrast agent imaging (USCAI) [3] has generated increased attention in recent years. As a result of the compressibility of microbubbles and the large acoustic impedance difference between them and the surrounding tissue, USCAI can greatly improve the contrast (CR) and contrast-to-tissue ratio (CTR) of a clinical ultrasound image. The detection rate, sensitivity, and specificity with which small lesions can be detected can therefore be greatly increased [4; 5]. Plane wave imaging (PWI) [6] has a great advantage over traditional B-mode imaging for USCAI. First, PWI can significantly reduce the destruction of microbubbles due to its low mechanical index. Second, PWI can track fast-moving microbubbles due to its high frame rate. However, poor imaging quality limits the clinical application of PWI. A large proportion of novel USCAI technologies [7; 8] appears to focus on the improvement of PWI imaging quality. Most of these existing methods enhance the image CTR by utilizing the abundant harmonic signals produced by UCAs. Generally speaking, the mainstream USCAI technologies can be classified into two categories: pulse coding [9] and bubble wavelet transformation (BWT) [10; 11]. Pulse coding focuses on the transmitting end as it either changes the number of the transmit pulse, transmit phase, transmit frequency, or transmit amplitude. Pulse inversion (PI) [12], amplitude modulation (AM) [13], chirp encoded excitation [14], and Golay\encoded excitation [15] are typical representatives of such methods. Since the response of UCA is represented as harmonic signals while that of tissue represents predominantly fundamental signals, the tissue signal can be removed by PI and AM technology. Chirp-encoded excitation emits a long sequence with the frequency variation over time. Studies have shown that chirp excitation has the ability to strengthen the harmonic signals and lower the sub-harmonic generation threshold [16]. However, the matched filter is needed in the receiving end to decode the signal, which adds complexity. Bubble wavelet transformation (BWT) is a novel type of USCAI technology proposed by [PERSON] et al. [10; 11]. BWT is utilized to analyze the correlation between the mother bubble wavelet and the received radio frequency (RF) signals. The constructed bubble wavelet obtained by simulating the microbubble model was highly correlated with the signals of microbubbles and has few similarities with the signals from surrounding tissues. The ability of BWT to enhance the imaging CTR has been validated by in vivo experiments. A mother wavelet was constructed by microbubble model simulation. The RF signals were then processed by the continuous wavelet transformation and a series of coefficient matrices was obtained. A better image quality and an enhancement of 6.0 dB in CTR can be obtained with BWT [11] while ensuring the high frame rate of PWI. Both the pulse coding and BWT improved the CTR in the time-frequency domain. Under a low mechanical index, tissue produces a predominantly linear response and, thus, it is feasible to distinguish tissue and UCA according to their frequency components. The non-linear distortion of waveforms and the spectrum overlap between the tissue and UCA is an unfavorable factor. In this paper, we take the tissue and UCA differences in both the frequency and spatial domains into consideration. PWI was used to improve the imaging frame rate and ensure the stability of UCA. A bubble wavelet based on the Doinikov model was firstly constructed. BWT was then applied to strengthen the UCA region and weaken the tissue region.