Combining imaging modalities has potential value in research and the clinical practice of medicine. Current methods of combining imaging modalities have limitations. They integrate the hardware of two modalities, a setup which requires highly specialized technical expertise, or using post-processing computer algorithms, a process performed post facto
). A fully integrated system for co-registering real-time US to any imaging modality is now commercially available; however the reliability of the system for vascular use has not been tested.
We first tested the reproducibility of the US system ex vivo and showed excellent agreement (ICC >0.99) between the LOGIQ E9 co-registration and manual registration methods. We also found very low bias between the two methods (<3 frames difference between methods) with the 95% limits of agreement not exceeding the upper 95% estimate of US frames indexed per MRI slice. Therefore, the LOGIQ E9 co-registration method using the GPS-like system reliably co-registers real-time US with MRI of CEA specimens.
Then, we explored the use of the co-registration system for improving carotid intima-media thickness (C-IMT) measurements. We evaluated the use of the US system for creating 3D US maps of the carotid artery, which were then used as references to guide image acquisition in similar planes/ angles during subsequent imaging. We found that inter-visit repeatability was consistently higher using the GPS-like technology than using the traditional Meijer’s arc. Intra-reader repeatability and inter-reader reproducibility was also consistently high for the GPS-like technology. It must be noted that both US methods were not ECG-gated which in turn could have further improved the reproducibility of the CIMT measurements. Finally, image resolution was noted to be qualitatively lower for these scans compared with scans acquired using the Meijer’s arc, probably because image enhancements were disabled with the GPS-like technology. However, image enhancements can be enabled with the GPS-like technology, as seen in the US-MRI co-registration protocol with patients having known carotid atherosclerosis. Therefore we believe that good (regular) quality images can be obtained using this technology. In spite of the image enhancements being disabled, we still found higher inter-visit correlations for C-IMT measurements with scans using the GPS-like technology than with those using the Meijer’s arc. Overall our findings suggest that use of the GPS-like technology can improve the reproducibility of C-IMT measurements, and provide a basis for improving reliability of serial C-IMT comparisons.
Finally, we evaluated US-MRI in vivo co-registration in a small number of patients with known carotid atherosclerosis who were participating in an MRI study. The results in this pilot analysis were consistent with the ex vivo experiment. These results from the pilot in vivo analyses suggest that the reliable co-registration observed ex vivo may translate to in vivo clinical applications as well and warrant further clinical exploration.
This “fusion” technology clearly has significant clinical and research applicability. From a clinical perspective, the technology can be used to map real-time US scans to previously acquired high-resolution MR image sets or images from other imaging modalities such as CT. A physician could therefore have the co-registered high-resolution images from the MRI or CT available for real-time navigation during a procedure to verify the anatomic location of interest and fuse the US information with the same images. Functional information gained from real-time US can be overlaid, or fused, with high-resolution images from different modalities for improving interpretation of the functional information. Another important clinical use could be recalling mapped US images in serial follow-up exams (as seen in our US-US registration experiment) to allow direct comparisons for changes (e.g., in dimensions) over time. With extension of the same technology to cardiac imaging one could think of the many potential scenarios where this technology will have clinical utility.
However, we must recognize that imaging cardiovascular structures which may pulsate, contract or twist will bring with it a set of challenges. For example, what would happen if the heart rate changes between the time of the MR/ CT imaging and the ultrasound? It is possible that using electrocardiography (ECG)-gating and developing computer algorithms that match phases of the cardiac cycle for volumetric comparisons one could circumvent this issue; however further work is needed to understand all the issues with such a scenario. Another potential issue (which is an issue with any current clinical imaging) would be irregular heart rate. Ultimately, the challenges for clinical implementation may depend on the purpose for fusing MR/ CT imaging with real-time US. If one desires high precision from the fusion say for example in a biopsy or a stent graft implantation perfect co-registration will be required. On the other hand if one is primarily interested in the functional significance of an anatomical finding or in harnessing the advantages specific to each imaging modality in evaluating an anatomical structure or its function, these challenges (e.g., pulsatility, etc.) may be less of an issue and the technology in its current form could readily be used to bring images from another imaging modality to ultrasound. For example, an area of interest not clearly seen on routine ultrasonography may be identified on MR/ CT imaging and its functional significance then interrogated after fusion with ultrasonography
Finally additional factors that will be critical in the adaptation of this technology and dictate clinical scenarios in which one will use this technology include the additional time required for the registration/fusion and technologist training in other imaging modalities, i.e. being able to identify orientation and anatomy in other imaging modalities, as evidenced by our mis-identification of one carotid artery during our in vivo ultrasound-MRI co-registration.
For research, prospective clinical studies using B-mode US imaging are often criticized for poor scan plane reproducibility of anatomic locations, which can become highly significant for making very small measurements (17
). For example, common C-IMT requires a measurement precision on the order of ~0.001 mm to detect progression, a precision that is sensitive to scan plane reproducibility (18
). The American Society of Echocardiography recognized such an issue when releasing its 2008 C-IMT Consensus Statement and suggested the use of a Meijer’s Arc, an external reference system, to improve its reproducibility (19
). However, US scans using the Meijer’s Arc are still subject to scan plane variations (although to a lesser degree). Furthermore, the C-IMT’s of the internal carotid artery and bifurcation suffer greater inter-observer variability than C-IMT’s of the common carotid and may benefit from improved scan plane reproducibility as well (20
). Allowing co-registration may further improve the reproducibility of these measurements.
Our C-IMT study comparing this technology with traditional methods using the Meijer’s arc support the use of this technology for fulfilling a role in improving scan plane reproducibility for C-IMT measures and for general prospective studies using ultrasound imaging. Similarly, this technology could have great use in studies that use echocardiographic end points to ensure that measurements are made in similar planes. At the very least, the technology may simply allow for serial follow-up of an area of interest on US and allow for comparisons of real-time US with other imaging modalities.
This study and the technology used have several limitations. As with any new medical technology, time must be spent learning the implementation of the GPS-like technology in a clinical setting. The system required initial registration of readily identifiable image features, making it semi-automated. The DC magnetic array should not be moved once the initial registration process has been completed; otherwise the probe position would not be detected correctly. Similarly, once images are registered, the patient cannot be allowed to move either. Also, the co-registration system is currently rigid and non-elastic and cannot account for changes in anatomic position (e.g. flexion, extension, rotation of joints). Thus, patients must be positioned in a manner similar to that on the co-registered image modality (e.g., MRI or CT), which may not be the optimal position for US imaging. Additionally, confirmation of co-registration using manual methods can be complicated by US sweeps following a staggered back-and-forth path instead of following a continuous path in one direction. For the C-IMT study, images acquired with the GPS-like technology had lower resolution compared with those acquired with the Meijer’s arc due to image enhancements being disabled for our protocol.
From a study stand point, the sample sizes for all of our studies were small. Our ICC for measuring C-IMT from scans acquired with the Meijer’s arc was lower than has been previously reported since the LOGIQ E9 vascular US instrument we used did not have electrocardiography (ECG)-gating. We chose to use this system for both methods in order to reduce instrument related variability/ quality for CIMT measurement. However, it must be noted that the LOGIQ E9 vascular US systems now have ECG-gating capability.
A novel position-sensing technology that uses an electromagnetic array enables excellent real-time registration of US scan frames to MRI data and stored 3D US references. This technology may have applications to other imaging modalities and to clinical and research use.