MRI biomarkers associated with guide wire puncture forces required to cross ex-vivo human peripheral arterial chronic total occlusions
Trisha Roy1,2, Garry Liu1, Noor Shaikh1, Kevan Anderson1, Nicolas Yak1, Xiuling Qi1, Andrew Dueck1,2, and Graham Wright1,3

1Schulich Heart Program and the Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 2Division of Vascular Surgery, University of Toronto, Toronto, Canada, 3Department of Medical Biophysics, University of Toronto, Toronto, Canada

Synopsis

Percutaneous vascular interventions (PVI) for treating peripheral arterial disease (PAD) have poor outcomes with high re-intervention and failure rates. Not all lesions are amenable to PVI, but predicting failure is difficult. While CT can identify heavily calcified lesions, current imaging offers limited differentiation between hard and soft PAD plaques, which impacts procedural success. This study demonstrates the feasibility of using MRI biomarkers to characterize plaque components in ex-vivo human peripheral arteries with histologic and microCT validation. We demonstrate that significantly higher puncture forces are required to cross non-calcified “hard” chronic total occlusions (CTOs) compared to “soft” CTOs, as classified by these MRI biomarkers.

Target Audience

MR vascular imaging researchers, interventional radiologists, interventional cardiologists, vascular surgeons

Purpose

Many of the challenges associated with planning and performing lower-extremity percutaneous vascular interventions (PVI) are associated with limited visualization. X-ray fluoroscopy does not allow the visualization of the vessel wall or plaque components. This information may assist with predicting the success of an intervention, navigation within an occlusion, and wire/device selection.

We hypothesize that MRI can characterize peripheral arterial disease (PAD) plaque components and their associated mechanical properties. Understanding PAD plaque composition may help in planning and performing PVI by identifying soft lesion components to facilitate guide wire passage. We aim to develop and validate MRI methods for characterizing PAD lesions to ultimately use this information to plan PVI for patients.

Methods

MRI was performed on 31 excised human peripheral arterial plaques from 6 patients who underwent amputation. Each sample was imaged at 7 Tesla at high resolution (75μm3 voxels) to produce 3D T2-weighted (T2W) and Ultrashort Echo Time (UTE) images. For T2W imaging, a fast spin-echo sequence with an echo-train length of 8 and an effective TE of 47 ms was used. For UTE imaging, a gradient-echo radial sequence with a TE of 20μs was used. 15 samples were studied to validate MR biomarkers for the following components (T2W, UTE): lumen (∅,∅), fat (+, ≈), thrombus (∅, +), loose fibrous tissue (≈, ≈), dense fibrous tissue/collagen (∅,≈), and calcium (∅,-), where ∅ means no signal, and -,≈,+ mean hypo-, iso-, an hyper-intense versus muscle respectively. Tissue classes were validated with microCT and histology.

The remaining 16 lesions were all chronic total occlusions (CTOs) and were used for guide wire force-displacement testing. CTOs with MR imaging signatures corresponding to fat, thrombus or those with microchannels were classified as “soft”. CTOs with loose fibrous tissue imaging signatures were classified as “intermediate”. CTOs with dense fibrous tissue/collagen MR imaging signatures were classified as “hard”. Guide wire crossing studies were performed on each sample. A 2kg load cell advanced the back end of a 0.035” Lunderquist® Extra Stiff (Cook Medical) guide wire at a fixed displacement rate of 0.05mm/s through the CTO, and the forces required to cross the lesion were measured.

Results

MRI biomarkers for “hard”, “intermediate” and “soft” CTOs correlated with guide wire force-displacement testing. Though densely calcified plaques were studied for sequence validation (Figure 1), there were no densely calcified CTOs in the subset of samples that underwent force-displacement testing. Preliminary testing of densely calcified plaques failed mechanical testing likely because they required puncture forces greater than 20N (the upper limit of our current experimental set-up). Non-calcified hard CTOs (n=2) required an average puncture force of 1.92N ± 0.83 (Figures 2 and 3). Intermediate CTOs (n=10) required an average puncture force of 0.36N ± 0.21. Soft CTOs (n=4) required an average puncture force of 0.05N ± 0.02. There was a statistically significant difference between groups as determined by one-way ANOVA (F(2,13) = 30.407, P <.05).

Discussion and Conclusion

PVI offers an attractive, minimally invasive approach to treating PAD, but not all lesions are amenable to PVI. Densely calcified lesions are resistant to dilatation, have higher failure and complication rates1 with PVI and are typically recommended for bypass surgery2. Though current clinical imaging modalities can characterize calcium well, they offer limited visualization of non-calcified hard plaques, which also influence procedural success3. The results of this study demonstrate the potential of using high-resolution MRI to differentiate densely calcified plaques, non-calcified hard plaques and soft plaques to determine ease of guide wire crossing. This study provides a foundation for future in-vivo studies on predicting the lesion crossability of various PAD plaque types from MRI data sets of patients who undergo PVI.

Acknowledgements

This study was supported by funds from the Canadian Institutes of Health Research.

References

1. Das T, Mustapha J, Indes Jeffrey, et al. The CONFIRM series, a prospective multicenter registry. Catheter Cardiovasc Interv. 2014:83(10):115-22.

2. Strauss BH, Osherov AB, Radhakrishnan S, et al. Collagenase Total Occlusion-1 (CTO-1) trial. Circulation. 2012;125(3):522-528.

3. TASC Steering Committee*. A supplement to the inter-society consensus for the management of peripheral arterial disease (TASC II). J Endovasc Ther. 2015;22(5):663-677.

Figures

1. MRI biomarkers of popliteal artery plaque components with histology and µCT validation. A) T2W images differentiate smooth muscle (blue) from fat (orange). Thrombus (red) and the calcified nodule with interspersed collagen (pink) are not seen due to short T2. B-D) UTE images differentiate hypointense calcium from isointense collagen fragments and hyperintense thrombus (using smooth muscle as reference intensity). D) Histology with Movat’s pentachrome staining. E-G) µCT of calcium nodule

2. MRI biomarkers of peroneal artery non-calcified hard CTO. T2W does not show dense collagen due to short T2. UTE image show dense collagen as isointense using smooth muscle as reference intensity.

3. Puncture forces of CTO types and sample force-displacement curve of CTO shown in Figure 2



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
0967