A novel technology for reversible fallopian tubal occlusion using a reverse thermo-responsive polymer-Preliminary results from a rabbit animal study.

OBJECTIVES: To determine if PF-88, a reverse thermo-responsive polymer designed to create a gel at body temperature and liquefy at a lower temperature (21°C) can reversibly occlude the fallopian tubes in rabbits. STUDY DESIGN: Mature female New Zealand White rabbits underwent laparotomy and placement of 22-gage catheter into the lumen of the distil uterine horns for evaluation of tubal patency by fluoroscopy using radio opaque contrast and treatment with PF-88. In the Acute Phase group (n = 5) after PF-88 treatment we immediately cooled the serosal surface of the tube with ice for 90 seconds to liquify the gel then reassessed patency. In the Survival Phase groups, animals recovered from the initial surgery and then underwent a second procedure for evaluation of tubal occlusion and reversibility at 4 (n = 3), 14 (n = 2), and 28 (n = 3) weeks after the initial procedure. We compared the histologic appearance of the treated fallopian tubes to untreated controls (n = 3). RESULTS: In the Acute Phase, we found all 10 fallopian tubes patent on initial evaluation, occluded following treatment with PF88, and patent following re-liquification by chilling. Animals in the Survival Group, all but one of the treated tubes appeared blocked at follow-up and patent following chilling. The treatment failure occurred in an animal in the 4-week group. Tubes treated with PF88 showed no histologic evidence of residual material or damage after removal of the polymer. CONCLUSION: The PF-88 reverse thermo-responsive polymer demonstrated the ability to reversibly block fallopian tubes for up to 28 weeks. IMPLICATIONS: The demonstration of reversible occlusion of the fallopian tube of rabbits using PF-88, a thermo-responsive reverse polymer, support additional studies to evaluate the potential of this polymer as a contraceptive in women.

In vivo noninvasive three-dimensional (3D) assessment of microwave thermal ablation zone using non-contrast-enhanced x-ray CT.

PURPOSE: To develop an image processing methodology for noninvasive three-dimensional (3D) quantification of microwave thermal ablation zones in vivo using x-ray computed tomography (CT) imaging without injection of a contrast enhancing material. METHODS: Six microwave (MW) thermal ablation procedures were performed in three pigs. The ablations were performed with a constant heating duration of 8 min and power level of 30 W. During the procedure images from sixty 1 mm thick slices were acquired every 30 s. At the end of all ablation procedures for each pig, a contrast-enhanced scan was acquired for reference. Special algorithms for addressing challenges stemming from the 3D in vivo setup and processing the acquired images were prepared. The algorithms first rearranged the data to account for the oblique needle orientation and for breathing motion. Then, the gray level variance changes were analyzed, and optical flow analysis was applied to the treated volume in order to obtain the ablation contours and reconstruct the ablation zone in 3D. The analysis also included a special correction algorithm for eliminating artifacts caused by proximal major blood vessels and blood flow. Finally, 3D reference reconstructions from the contrast-enhanced scan were obtained for quantitative comparison. RESULTS: For four ablations located >3 mm from a large blood vessel, the mean dice similarity coefficient (DSC) and the mean absolute radial discrepancy between the contours obtained from the reference contrast-enhanced images and the contours produced by the algorithm were 0.82 ± 0.03 and 1.92 ± 1.47 mm, respectively. In two cases of ablation adjacent to large blood vessels, the average DSC and discrepancy were: 0.67 ± 0.6 and 2.96 ± 2.15 mm, respectively. The addition of the special correction algorithm utilizing blood vessels mapping improved the mean DSC and the mean absolute discrepancy to 0.85 ± 0.02 and 1.19 ± 1.00 mm, respectively. CONCLUSIONS: The developed algorithms provide highly accurate detailed contours in vivo (average error < 2.5 mm) and cope well with the challenges listed above. Clinical implementation of the developed methodology could potentially provide real time noninvasive 3D accurate monitoring of MW thermal ablation in-vivo, provided that the radiation dose can be reduced.

Optical flow and image segmentation analysis for noninvasive precise mapping of microwave thermal ablation in X-ray CT scans - ex vivo study.

PURPOSE: To develop image processing algorithms for noninvasive mapping of microwave thermal ablation using X-ray CT. METHODS: Ten specimens of bovine liver were subjected to microwave ablation (20-80 W, 8 min) while scanned by X-ray CT at 5 s intervals. Specimens were cut and manually traced by two observers. Two algorithms were developed and implemented to map the ablation zone. The first algorithm utilises images segmentation of Hounsfield units changes (ISHU). The second algorithm utilises radial optical flow (ROF). Algorithm sensitivity to spatiotemporal under-sampling was assessed by decreasing the acquisition rate and reducing the number of acquired projections used for image reconstruction in order to evaluate the feasibility of implementing radiation reduction techniques. RESULTS: The average radial discrepancy between the ISHU and ROF contours and the manual tracing were 1.04±0.74 and 1.16±0.79mm, respectively. When diluting the input data, the ISHU algorithm retained its accuracy, ranging from 1.04 to 1.79mm. By contrast, the ROF algorithm performance became inconsistent at low acquisition rates. Both algorithms were not sensitive to projections reduction, (ISHU: 1.24±0.83mm, ROF: 1.53±1.15mm, for reduction by eight fold). Ablations near large blood vessels affected the ROF algorithm performance (1.83±1.30mm; p < 0.01), whereas ISHU performance remained the same. CONCLUSION: The two suggested noninvasive ablation mapping algorithms can provide highly accurate contouring of the ablation zone at low scan rates. The ISHU algorithm may be more suitable for clinical practice as it appears more robust when radiation dose reduction strategies are employed and when the ablation zone is near large blood vessels.

Tissue shrinkage in microwave thermal ablation: comparison of three commercial devices.

PURPOSE: To evaluate, characterise and compare the extent of tissue shrinkage induced from three different commercial microwave ablation devices, and to elucidate the mechanism behind the distinctive performances obtained. MATERIALS AND METHODS: Microwave ablation (N = 152) was conducted with three different commercial devices on cubes of ex vivo liver (10-40 ± 2 mm/side) embedded in agar phantoms. 50-60 W was applied for 1-10 min duration. Pre- and post-ablation dimensions of the samples, as well as the extent of carbonisation and coagulation were measured and correlated. ANOVA was performed to evaluate statistical significance. RESULTS: For all devices, logarithmic correlations with time were observed for both tissue shrinkage (R2 = 0.84-1.00) and induced carbonisation (R2 = 0.73-0.99) radially to the antenna axis. Along the longitudinal axis of the antenna, for two of the devices shrinkage did not appreciably change with time (p > 0.05), yet carbonisation increased linearly (R2 = 0.57-0.94). For the third fully internally-cooled device, both carbonisation and shrinkage showed logarithmic trends (R2 = 0.85-0.98 and R2 = 0.78-0.94, respectively) based upon delayed carbonisation appearing only 5 min into ablation and onward. For all devices, non-uniform shrinkage was noted within the coagulated area increasing from the boundary of the ablated area (14%) to the limit of carbonisation (39%) in a linear fashion (R2 = 0.88) Conclusions: Microwave ablation device construction can alter the extent of post-ablation coagulation and tissue shrinkage. Given that tissue shrinkage in the coagulated area shows non-uniform behaviour, observed differences can be attributed in part to the applicator cooling system that alters the ablation temperature profile.

Microwave ablation of primary and secondary liver tumours: ex vivo, in vivo, and clinical characterisation.

PURPOSE: The aim of this study was to compare the performance of a microwave ablation (MWA) apparatus in preclinical and clinical settings. MATERIALS AND METHOD: The same commercial 2.45 GHz MWA apparatus was used throughout this study. In total 108 ablations at powers ranging from 20 to 130 W and lasting from 3 to 30 min were obtained on ex vivo bovine liver; 28 ablations at 60 W, 80 W and 100 W lasting 5 and 10 min were then obtained in an in vivo swine model. Finally, 32 hepatocellular carcinomas (HCCs) and 19 liver metastases in 46 patients were treated percutaneously by administering 60 W for either 5 or 10 min. The treatment outcome was characterised in terms of maximum longitudinal and transversal axis of the induced ablation zone. RESULTS: Ex vivo ablation volumes increased linearly with deposited energy (r2 = 0.97), with higher sphericity obtained at lower power for longer ablation times. Larger ablations were obtained on liver metastases compared to HCCs treated with 60 W for 10 min (p < 0.003), as ablation diameters were 4.1 ± 0.6 cm for metastases and 3.7 ± 0.3 cm for HCC, with an average sphericity index of 0.70 ± 0.04. The results on the in vivo swine model at 60 W were substantially smaller than the ex vivo and clinical results (either populations). No statistically significant difference was observed between ex vivo results at 60 W and HCC results (p > 0.08). CONCLUSIONS: For the selected MW ablation device, ex vivo data on bovine liver was more predictive of the actual clinical performance on liver malignancies than an in vivo porcine model. Equivalent MW treatments yielded a significantly different response for HCC and metastases at higher deposited energy, suggesting that outcomes are not only device-specific but must also be characterised on a tissue-by-tissue basis.

Noninvasive microwave ablation zone radii estimation using x-ray CT image analysis.

PURPOSE: The aims of this study were to noninvasively and automatically estimate both the radius of the ablated liver tissue and the radius encircling the treated zone, which also defines where the tissue is definitely untreated during a microwave (MW) thermal ablation procedure. METHODS: Fourteen ex vivo bovine fresh liver specimens were ablated at 40 W using a 14 G microwave antenna, for durations of 3, 6, 8, and 10 min. The tissues were scanned every 5 s during the ablation using an x-ray CT scanner. In order to estimate the radius of the ablation zone, the acquired images were transformed into a polar presentation by displaying the Hounsfield units (HU) as a function of angle and radius. From this polar presentation, the average HU radial profile was analyzed at each time point and the ablation zone radius was estimated. In addition, textural analysis was applied to the original CT images. The proposed algorithm identified high entropy regions and estimated the treated zone radius per time. The estimated ablated zone radii as a function of treatment durations were compared, by means of correlation coefficient and root mean square error (RMSE) to gross pathology measurements taken immediately post-treatment from similarly ablated tissue. RESULTS: Both the estimated ablation radii and the treated zone radii demonstrated strong correlation with the measured gross pathology values (R(2) ≥ 0.89 and R(2) ≥ 0.86, respectively). The automated ablation radii estimation had an average discrepancy of less than 1 mm (RMSE = 0.65 mm) from the gross pathology measured values, while the treated zone radii showed a slight overestimation of approximately 1.5 mm (RMSE = 1.6 mm). CONCLUSIONS: Noninvasive monitoring of MW ablation using x-ray CT and image analysis is feasible. Automatic estimations of the ablation zone radius and the radius encompassing the treated zone that highly correlate with actual ablation measured values can be obtained. This technique can therefore potentially be used to obtain real time monitoring and improve the clinical outcome.

Planar strain analysis of liver undergoing microwave thermal ablation using x-ray CT.

PURPOSE: To study the planar strain effects in liver during microwave (MW) thermal ablation as a means for tracking tissue expansion and contraction as a method for improving ablation monitoring. METHODS: 1.4 mm circular metallic markers were inserted into 16 ex-vivo bovine fresh liver specimens, that were subsequently ablated (with the markers inside the specimen) by 40 W of microwave energy, for 1, 2, 3, 6, and 10 min. The markers were tracked during the ablation using an x-ray CT scanner. Images were acquired every 5-10 s enabling determination of the markers' coordinates over time. The 2D principal strains were calculated for triangles formed by subgroups of three markers, and their planar strain index, Ω, was plotted vs time. In addition, the radial distance of the markers from the antenna was measured at the end of each ablation. Subsequently, the tissue was sliced parallel to the imaged planes and the ablation zone was traced and digitized. The average ablation radius was then computed and compared to the radial distance. RESULTS: The planar strain, Ω(t), profile demonstrated an ascending pattern until reaching a maximum at about 180 s, with a mean peak value (Ω = 1.31 ± 0.04) indicating tissue expansion. Thereafter, Ω progressively declined over the remaining duration of the ablation treatment, indicating tissue contraction. Furthermore, when plotting the ablation size vs time and the markers' mean radial distance vs time, it was found that the two curves intercepted at a time corresponding to the time of peak planar strain. CONCLUSIONS: By detecting the point of maximal planar strain in tissues during MW application, it is possible to noninvasively identify the location of the ablation zone front. The fact that the liver tissue proximal to the ablated zone expands during the first part of the treatment and then contracts when the ablation front reaches it, may serve as an index for monitoring the thermal treatment.

Characterisation of tissue shrinkage during microwave thermal ablation.

PURPOSE: The aim of this study was to characterise changes in tissue volume during image-guided microwave ablation in order to arrive at a more precise determination of the true ablation zone. MATERIALS AND METHODS: The effect of power (20-80 W) and time (1-10 min) on microwave-induced tissue contraction was experimentally evaluated in various-sized cubes of ex vivo liver (10-40 mm ± 2 mm) and muscle (20 and 40 mm ± 2 mm) embedded in agar phantoms (N = 119). Post-ablation linear and volumetric dimensions of the tissue cubes were measured and compared with pre-ablation dimensions. Subsequently, the process of tissue contraction was investigated dynamically during the ablation procedure through real-time X-ray CT scanning. RESULTS: Overall, substantial shrinkage of 52-74% of initial tissue volume was noted. The shrinkage was non-uniform over time and space, with observed asymmetry favouring the radial (23-43 % range) over the longitudinal (21-29%) direction. Algorithmic relationships for the shrinkage as a function of time were demonstrated. Furthermore, the smallest cubes showed more substantial and faster contraction (28-40% after 1 min), with more considerable volumetric shrinkage (>10%) in muscle than in liver tissue. Additionally, CT imaging demonstrated initial expansion of the tissue volume, lasting in some cases up to 3 min during the microwave ablation procedure, prior to the contraction phenomenon. CONCLUSIONS: In addition to an asymmetric substantial shrinkage of the ablated tissue volume, an initial expansion phenomenon occurs during MW ablation. Thus, complex modifications of the tissue close to a radiating antenna will likely need to be taken into account for future methods of real-time ablation monitoring.