Real-time magnetic resonance imaging-guided cryoablation of the pulmonary veins with acute freeze-zone and chronic lesion assessment

Abstract

Aims: The goals of this study were to develop a method that combines cryoablation with real-time magnetic resonance imaging (MRI) guidance for pulmonary vein isolation (PVI) and to further quantify the lesion formation by imaging both acute and chronic cryolesions.

Methods and results: Investigational MRI-compatible cryoablation devices were created by modifying cryoballoons and cryocatheters. These devices were used in canines (n = 8) and a complete series of lesions (PVI: n = 5, superior vena cava: n = 4, focal: n = 13) were made under real-time MRI guidance. Late gadolinium enhancement (LGE) magnetic resonance imaging was acquired at acute and chronic time points. Late gadolinium enhancement magnetic resonance imagings show a significant amount of acute tissue injury immediately following cryoablation which subsides over time. In the pulmonary veins, scar covered 100% of the perimeter of the ostium of the veins acutely, which subsided to 95.6 ± 4.3% after 3 months. Focal point lesions showed significantly larger acute enhancement volumes compared to the volumes estimated from gross pathology measurements (0.4392 ± 0.28 cm3 vs. 0.1657 ± 0.08 cm3, P = 0.0043). Additionally, our results with focal point ablations indicate that freeze-zone formation reached a maximum area after 120 s.

Conclusion: This study reports on the development of an MRI-based cryoablation system and shows that with acute cryolesions there is a large area of reversible injury. Real-time MRI provides the ability to visualize the freeze-zone formation during the freeze cycle and for focal lesions reaches a maximum after 120 s suggesting that for maximizing lesion size 120 s might be the lower limit for dosing duration.

Figures

Figure 1

Real-time MRI showing the anatomy of heart (A). Imaging plane along the four chamber view of the heart. The inflated balloon catheter is centred at z = 0 mm (C). Important landmarks and structures of the heart have been labelled in red. The lateral edges of the cryoballoon are visible in planes z = 7.6 mm (B) and z = −11.3 (D) mm and highlighted by blue arrowheads. Scale bar is 1 cm. The balloon is in the left atrium. LA, left atrium; LV, left ventricle; MRI, magnetic resonance imaging; RA, right atrium; RSPV, right superior pulmonary vein; RV, right ventricle.

Figure 2

Real-time MRI validation of PV occlusion. (A) Placement of the catheter and cryoballoon before injection of contrast. (B) Contrast injected from the distal tip of the balloon and confirms occlusion of the RSPV by the inflated cryoballoon. Scale bar is 1 cm. See Supplementary material online for the full video of contrast injection. MRI, magnetic resonance imaging; PV, pulmonary vein; RSPV, right superior pulmonary vein.

Figure 3

Real-time MRI of PV isolation. (A) Position of the deflated balloon catheter (centre of red circle) can be seen at t = −10 s. (B) Growth of signal void region corresponding to cryoballoon and frozen tissues can be monitored from t = 0 s. The balloon diameter is 2.29 cm. (C) The time point where the freeze-zone is at its maximal diameter, t = 180 s. The balloon diameter is 2.5 cm. (D) Graph showing the area of the freeze-zone. Scale bars represent 5 cm. See Supplementary material online for an image and video of another example of cryoablation. MRI, magnetic resonance imaging; PV, pulmonary vein.

Figure 4

Real-time MRI monitoring Freezor Max focal ablations. (A) Short-axis view of the heart with the Freezor Max catheter (arrow) in position at the start of ablation. (B) Short-axis view of the heart showing the freeze-zone in (A) after 120 s of cryoablation. (C) Growth of ablation in A–B over time and normalized to the area at t = 0 s. (D) Four chamber view of the heart with the Freezor Max catheter in position at the start of ablation. (E) Four chamber view of the heart showing the freeze-zone in (D) after 240 s of cryoablation. (F) Growth of ablation in D–E over time and normalized to the area at t = 0 s. (G) Mean and standard deviation of the average normalized growth of 2 min ablations (n = 5, red xs) vs. 4 min ablations (n = 5, turquoise squares). Scale bars in RT-MR images represent 5 cm. LV, left ventricle; MRI, magnetic resonance imaging; PV, pulmonary vein; RV, right ventricle.

Figure 5

Representative LGE images of the same LA lesion at acute (A) and 3-month chronic (B) time points after cryoablation. White arrows point to LSPV scar enhancement. (C) Gross pathology of the LA after the heart was fixed. Visible scar surrounding both the right and left PVs (black arrows). (D) Gross pathology of the transmural cross section of the LA wall from the fixed heart near the LSPV. Red arrowhead points to endocardium, red arrow points to epicardium. (E) Histology of the same region shown in D. Red arrowhead and arrows point to the same locations in E and D. White scale bars in MRIs and gross pathology represent 1 cm, black scale bar in histology represents 1 mm. LA, left atrium; LAA, left atrial appendage; LSPV, left superior pulmonary vein; LV, left ventricle; LGE, late gadolinium enhancement; PV, pulmonary vein; RA, right atrium; RSPV, right superior pulmonary vein; RV, right ventricle.

Figure 6

3D reconstructions of the LA lesion shown in Figure 4. View is oriented so we are looking parallel the longitudinal axis of the LSPV lumen from inside of the LA. White Xs mark the lumen of the LSPV. (A) The segmented scar from the acute LGE scan; (B) the same scar from the 3 month follow-up, chronic scan. Scale bars represent 5 mm. A slice of acute and chronic LGE MRI for these lesions is shown in Figure 5A and B, respectively. (C and D) Another orthogonal slice for the same acute and chronic lesions, respectively. (E) Summary data comparing the percent circumferential scar in SVCs (n = 4) and PVs (n = 5) at both acute and chronic time points. LA, left atrium; LGE, late gadolinium enhancement; LSPV, left superior pulmonary vein; MRI, magnetic resonance imaging; PV, pulmonary vein; SVC, superior vena cava.

Figure 7

(A) Acute LGE MRI showing an RV lesion highlighting the enhanced area (turquoise) and the MVO area (red). (B) LGE MRI showing the same lesion at a chronic time point (green). (C) Gross histology of the same lesion after explanation. Scale bars represent 1 cm. The graphs show summary data (n = 13) of the volumes and depths of the acute enhancement region, acute MVO region, and the chronic enhancement region. Brackets indicate significance of P < 0.05. LGE, late gadolinium enhancement; MRI, magnetic resonance imaging; MVO, microvascular obstruction; RV, right ventricle.