Ultrasonographic monitoring and early diagnosis of stroke

The defocusing effect of the skull strongly limits the transcranial imaging capabilities of commercial ultrasonic scanners. A fully programmable prototype dedicated to high resolution ultrasonic imaging of the brain has been constructed by Partner 5 in collaboration with Lecoeur Electronique (Subcontractor). An innovative aberration correction algorithm developed in the early stage of the UMEDS project has been successfully implemented on this new generation of ultrasonic scanner. Contrary to commercial scanners, the influence of the skull bone is evaluated during a calibration process and its defocusing effect is corrected at best. At the beginning of the project the calibration phase required 30min. Thanks to the last developments, this calibration phase decreased down to 1min. After the calibration process, it is possible to obtain real time images by storing the set of emission signals in the electronics. High resolution in vitro images have been obtained transcranially with this device. The resolution obtained through the skullbone is comparable to the one obtained without the presence of the skull: it means that the skull bone has been ultrasonically erased. This is a technical breakthrough in ultrasonic transcranial imaging. Furthermore, real time capabilities have been implemented in September 2005, allowing to proceed in the near future to real time in vivo imaging of the brain with the prototype.

Up to now commercial ultrasound contrast agents are blood-pool agents, meaning they are able to give a contrast of vascular compartments and to give information about blood perfusion and perfusion defects. With targeted microbubbles as contrast agents, a number of new applications are foreseen, in particular the possibility to detect a lesion, assess the importance of the lesion, as well as monitor the efficacy of treatments of the diseased areas. At this stage, the result described here can be used only by a research center willing to go further in the research and development process for this technology. The main innovative feature of these ultrasound contrast agents is that they will enable a clear detection of vascular lesion (location and size) rather than derived parameters such as blood perfusion. By using them repeatedly, they will enable a monitoring of treatment and follow-up of patients. It might represent also a cost-effective alternative to other imaging techniques such as MRI or computed tomography.

A novel ultrasound (US) echographic system has been designed and implemented by using state-of-the-art high-tech electronic devices. Main feature of the new system is the achievement of high levels of: 1. Integration (the prototype consists of a single electronic board of small dimensions -18x20cm- to be connected to any host PC through an USB 2.0 interface); 2. Programmability (i.e., capability of adapting to multiple applications, as it can hardly be found in commercially available US systems). In the UMEDS project, the system has been shown capable of performing automatic micro-embolic signal (MES) detection by using expert system theory. While testing the system on patients subject to cardiovascular surgical treatment, excellent sensitivity and specificity have been achieved. The high flexibility makes the system suitable in other US applications as, e.g., the early diagnosis of cardiovascular diseases through Doppler methods, the characterization of human tissues, the non-destructive testing of materials. Further applications, only requiring the development of dedicated software, could be considered. The board is easily reproducible (5 prototypes have been built and are currently tested in international laboratories). The system is of potential interest for all laboratories involved in ultrasound studies, either at research or clinical level.

A perfusion analysis software was designed on the basis of a pre-study to comply with the five following requirements: friendly user interface for easy clinical use, new software for automatic analysis of perfusion sequences, conventional parametric analysis of perfusion sequences for an easy comparison of the results of the new software with conventional tools, ability to accept all image formats of the consortium members and easy archiving of the results. Main developments included plug-ins (java and C language) coding for the commercial Pixies software, and specific tools for automatic masking, selection of motion free images in the sequence. The Famis software is implemented either as a step by step supervised process under the permanent control of the user or as an automatic one-step function. The system can be used both for research purposes either for clinical or pharmaceutical applications. Potential end users can be researchers or clinical staffs. The software is available as a CDROM providing the acquisition of the Pixies exploitation license. The capacity of the product is comparable to other pre-existing platforms concerning basic parametric imaging. The Famis parametric allows more insight in the time course and the spatial localization of perfusion parameters. A companion software developed in MATLAB can be used to improve significantly parametric and Famis imaging by removing from the acquisitions frames corrupted by the respiratory motion. The only condition is that a sufficiently high frame rate of the images. These software packages can be applied to perfusion acquisitions in other modalities such as Nuclear Imaging, Computerized Tomography or magnetic resonance imaging.

Identification of microemboli in the cerebral circulation using transcranial Doppler (TCD) ultrasound provides valuable clinical information, but currently micro-embolic signal (MES) detection and analysis are significantly limited as they rely mainly on costly off-line manual analysis by human experts. A knowledge-based system has been designed and implemented for automated identification and archival of MESs in real-time. Preliminary tests have been carried out to evaluate the system. The system hardware consists of a PC and a powerful digital signal processing (DSP) board. The signal-processing engine of the system contains an FFT-based spectral analysis unit and a MES detection unit utilizing expert system reasoning theory. The system extracts information in time, frequency and neighbourhood domains from input Doppler signals. The information is then further processed using an expert system blackboard structure. For MES archival, segments of the raw Doppler signal corresponding to each detected event are saved into a data file, together with all relevant information. Preliminary clinical tests have been carried out using Doppler signals obtained from carotid endarterectomy patients and healthy volunteers. The results have demonstrated a sensitivity of 93.6% and a specificity of 99.2%.

During the UMEDS grant the iU22/iE33 premium ultrasound systems have been designed and built by Philips with unique capabilities including real-time 3D imaging using matrix transducers, integrated quantification software, and voice control. Early in the grant the HDI-5000 was optimized for transcranial contrast imaging and evaluated by the UMEDS partners. Since the introduction of the iU22/iE33 products there have been two upgrades with contrast enhancements. Features for cerebral-vascular ultrasound available in 2006 will include: - Transcranial color Doppler on the S5-1 phased array with significantly better performance than the HDI 5000. - Advanced nonlinear processing contrast capability on the S5-1 for brain perfusion in real-time. - Contrast capability on the X3 matrix transducer which will be optimized for 3D brain perfusion. - Color flow optimized for contrast following a perfusion study. - Side-by-side nonlinear contrast imaging with fundamental tissue imaging. - QLab quantification software running on system and off cart. Real-time low MI imaging of brain perfusion through the intact skull in stroke patients is the most significant development. This capability has been clinically evaluated. It will open new avenues of clinical research and stroke care never before thought possible with ultrasound.

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