In this study we report on assessment of cryoablation tissue damage in the in vivo canine prostate with T1w and T2w MRI. Cryolesions created using different freezing protocols were analyzed at various post-ablation time intervals with MRI and histopathology to understand the MR appearance of the acute and chronic lesions and tissue regeneration. Lesions created in the prostate gland by cryoablation appear differently on the various MR imaging techniques as they heal. Compared to CE imaging, T1w and T2w imaging can be conveniently repeated acutely post-ablation, and can also be done between multiple freeze-thaw cycles. T1w and T2w imaging can provide additional evaluation of scar tissue formation and gland regeneration, along with the vascular information that CE provides.
The acute T2w lesion area lies between the CE-non perfused and the CE-hyperemic rim. For all lesions combined, the mean area of the CE non-perfused lesion was 69.6 mm2
, of the T2w lesion was 89.2 mm2
, and of the CE non-perfused lesion plus hyperemic rim was 114.5 mm2
. Similarly, a previous study showed that the necrosis area on histology also lies between the CE-non perfused and the CE-hyperemic rim in acute studies [15
]. From their results for all lesions combined, the mean area of the CE non-perfused lesion was 167 mm2
, of tissue necrosis was 187 mm2
, and of the CE non-perfused lesion plus hyperemic rim was 328 mm2
. This comparison of the T2w lesion area with the CE lesion area in conjunction with the CE comparison to histology in [15
], provides an indirect approach to understanding how the T2w lesion compares to histology. It adds to our knowledge of how the vascular injury depicted by CE MRI relates to the coagulation necrosis in tissue. Based on the combined results of these studies, T2w imaging can potentially also be a useful indicator of the area of damage. A direct comparison of the acute T2w lesion area with necrosis could not be performed in this study, and would be valuable to validate how accurately T2w imaging can predict the cryo treatment margins. Unfortunately the few cases for which both the acute T2w imaging and histology data was available, and the difficulty in matching the MR images with the histology slides limits this comparison. Future studies will include a comparison of lesion area on T2w imaging with necrosis on histology.
The T2w imaging visualized the lesion for a variety of freezing protocol parameters, though the signal intensity varied depending on these parameters. The T2w signal enhanced more for a smaller freeze area. We hypothesize that the T2w signal change is caused by fluid accumulation within the cryolesion from injured microvessels within and surrounding the lesion, and that in larger lesions the fluid is distributed over a larger volume, resulting in less T2w signal increase. The acute T2w signal analysis is complicated by the co-dependence of the freeze protocol parameters. More data is needed to separate out the effect of all these variables, to enable a multi-parametric analysis
The central hemorrhagic region of the cryolesion appears isointense or hypointense on acute T1w images, while the dark rim could be a combination of hemorrhage and edema. The T1w lesion was visible only in 6 dogs on imaging done immediately after cryoablation, though there was significant hemorrhage observed on pathology in all acute dogs. This could potentially be due to a delayed appearance of the T1w lesion on MRI. This delay in appearance was seen in 2 of our chronic studies, where the T1w lesion was not observed on day 0 but was visible on day 4 (dog 1) and day 14 (dog 2). Over time as erythrocytes break down and the hemorrhage is resolved, the lesion appearance evolves on T1w imaging. At day 7, the T1w lesion was hyperintense, indicating T1 shortening. Between day 7 and 21, the T1 lengthened. At day 53, the site of the lesion showed dense scar tissue, which was seen as a hypointense T1w lesion.
Acutely post-ablation (day 0), no differences were seen on T1w or T2w imaging between the various freeze protocols. The T1w lesion appeared hyperintense for both protocols at day 7. T2w imaging performed on day 7 however showed a difference in lesion appearance between the different protocols. A limited number of time points were imaged in this study, and it would be valuable to perform a longitudinal study with more imaging conducted between day 0-7 to resolve better the timeline of how the freezing protocols differ on T2w imaging.
The secretory epithelium that lines the prostatic glands is capable of undergoing regeneration as long as some basal cells and the structural basement membranes remain intact. At the edges of the cryolesions, where temperatures are not as cold, sub lethally damaged glands regenerate. Functionality of the glands, however, remains unclear. In addition it is unclear how closely the regenerative capability of canine prostate glands compares to the regenerative potential of human prostate tissue and prostate cancer.
In the skin model of wound repair, healing begins within approximately 24 hrs as the associated hemorrhage clots and inflammatory cells migrate to the site. Within 3-7 days, a bed of granulation tissue is established, while the formation of mature scar tissue may take several weeks [24
]. We have documented a similar time frame for healing in the cryolesioned prostate tissues.
In conclusion, T1-weighted and T2-weighted MRI can potentially be used to assess cryolesions and to monitor tissure response over time following cryoablation. Further refinement and interpretation of subtle differences noted between the various freezing protocols on the different imaging modalities is desirable.