Freezing and Frying Renal Cancers:

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1 Freezing and Frying Renal Cancers: An Imaging Menu for Radiologists to Understand Intra- and Post-Procedural Imaging Findings after Renal Tumor Ablation Heidi Coy BS, Michael Douek MD, Steven Raman MD Department of Radiological Sciences Ronald Reagan-UCLA Medical Center David Geffen School of Medicine at UCLA

2 DISCLOSURES Heidi Coy-None Michael Douek-None Steven Raman-None

3 OBJECTIVES 1. Review intraprocedural image findings of cryoablation, radiofrequency ablation, microwave ablation and irreversible electroporation of renal cell carcinoma in various imaging modalities 2. Describe surveillance image findings and define imaging characteristics of successful ablation 3. Define signs of tumor recurrence seen at longitudinal follow-up Target Audience: Trainees, Interventional Radiologists, Multidisciplinary Clinicians

4 BACKGROUND Renal Tumor Ablation: Patient Selection Patients with contraindications to surgery Patients with solitary kidneys Patients with prior surgical resections vhl patients with multiple tumors Or patients who just want Ablation!

5 BACKGROUND Renal Tumor Ablation: Importance of Multiphasic Imaging for Lesion Detection and Follow-up A dedicated four-phase renal mass protocol is best to differentiate small vascular lesions which may blend into the cortex in an early arterial phase (corticomedullary) and hypovascular lesions which may have delayed enhancement and will not be as apparent until a delayed phase (nephrographic and excretory) On Detector CT Unenhanced Scan Enhanced Scan Phases: Inject cc Omnipaque 3-4 cc/sec Bolus tracking 25 sec after aorta HU > 150 ) Corticomedullary phase scan (45 sec) Nephrographic phase scan (80-90 sec) Excretory phase scan (3 min) Unenhanced Corticomedullary Nephrographic Excretory

6 BACKGROUND Renal Tumor Ablation: Discrimination of Histological Subtypes on MDCT Prior work from our group has shown that renal cell carcinoma (RCC) subtypes and common benign RCC mimics have distinct absolute enhancement profiles across the four-phases on MDCT and in comparison to normal renal parenchyma, enabling clinicians to better stratify patients to the correct therapeutic pathway. CAD Mean Relative Lesion to Cortex Attenuation (%) Clear Cell RCC Oncocytoma Chromophobe RCC Papillary RCC Lipid Poor AML Unenhanced Corticomedullary Nephrographic Excretory Bar graph shows multiphasic CAD relative attenuation of clear cell RCCs (n=105), oncocytomas (n=41), chromophobe RCCs (n=18), papillary RCCs (n=45), and lipid-poor angiomyolipomas (n=14). Data points are mean CAD relative attenuation values for each phase. Relative attenuation= [(CAD absolute attenuation-cortex ROI)/cortex ROI] *100%. Error bars represent 95% CIs for the mean. CAD=Computer Aided Diagnosis. RCC=Renal Cell Carcinoma. AML=angiomyolipoma. Coy, Young, Raman et al. RSNA 2015

7 BACKGROUND Renal Tumor Ablation: Lesion Selection IDEAL: LESIONS <5CM POSTERIOR EXOPHYTIC CENTRAL LESIONS MORE DIFFICULT LESIONS: ANTERIOR AND MEDIAL LESIONS ADJACENT TO URETER OR UPJ

8 BACKGROUND Renal Tumor Ablation: Avoid Potential Complications GF nerve Ureter Duodenum

9 Ultrasound (US) Unparalleled precision BACKGROUND Imaging Guidance US Guidance/CT Monitoring MR Guidance Silverman, S. G. et al. Radiology 2005;236: Silverman, S. G. et al. Radiology 2005;236:

10 CRYOABLATION Ablative Technique and Imaging Guidance Relies on the Jewel Thomson effect to create an ice ball Placing one or more needle like cryoprobes (14-G-18G) directly into renal neoplasm under image guidance Cell death via freezing to <-40 o C followed by thawing Intracellular ice formation and osmotic imbalance resulting from extracellular ice formation Indirect cell death from induced microvascular damage and apoptosis Endocare

11 CRYOABLATION Intraprocedural Image Findings US is suboptimal compared to CT or MR because the developing ice ball obscures sound wave penetration resulting in small echogenic leading edge with a hypoechoic shadow deep to the leading edge at the lesion The ice ball is a uniformly hypodense (CT) or T1 hypointense (MR) ovoid sphere which ideally encompasses the entire lesions with a 5mm margin. Pre 2 min 6 min 10 min Immediate Post Courtesy Matt Callstrom, Mayo Clinic

12 CRYOABLATION Intraprocedural Image Findings Pre Freezing Thaw Courtesy: Fred Lee, UW Madison

13 CRYOABLATION Image Findings Immediately After Ablation CT IMAGING: During the acute period immediately following ablation, the treatment zone appears larger than the original tumor and infiltration in the fat surrounding the ablation zone may enhance The ablation zone has low attenuation, and emergence of the peripheral halo in perinephric fat surrounding the smaller high density ablated lesion can be see the first few months following cryoablation. a RCC in a 63 year old man treated with cryoablation. Diagnostic CT (a) shows an endophytic lesion. Immediately following cryoablation (b) there is a hypodense ablated lesion with stranding and enhancement within the perinephric fat. b MR IMAGING: Cryo-treated lesions appear variably T1 hyperintense or and T2 hypointense relative to the renal parenchyma. The peripheral halo of the ablation zone border after can be seen after contrast administration and surrounding fat retains signal on all sequences.

14 CRYOABLATION Successful Ablation and Surveillance Imaging Findings Lesion size progressively decreases over time to a greater degree than RF treated lesions Up to 32% of cryo-treated lesions may become undetectable over time Decreased stranding, hematomas & perinephric fluid Emergence of the peripheral halo in perinephric fat surrounding the smaller high density ablated lesion Pre 1 month 1 year 2 years In a 63 year old man, diagnostic CT shows an exophytic papillary RCC. 1 month post cyroablation, CT imaging shows stranding and a hypodense ablation zone. 1 year post cryoablation, significant decrease in ablation zone and lesion size, with residual curvilinear enhancement and stranding in in the perinephric fat. 2 years post cryoablation, significant decrease in ablation zone and lesion size, with reduced curvilinear enhancement and persistent stranding.

15 CRYOABLATION Signs of Recurrence Usually occurs within or adjacent to ablation zone Enlarging ablation zone Increased linear or nodular enhancement May also occur in: Renal vein Contralateral kidney Adrenal glands Lymph nodes Liver, lung, pleura or bones 1 month post 3 months post 6 months post A 67 year old man with an endophytic lesion treated with cryoablation. 1 month post-cryoablation surveillance MR imaging shows curvilinear enhancement within the ablated lesion. 3 months post-cryoablation surveillance MR imaging shows persistent curvilinear enhancement and a subtle increase in lesion size. 6 months post-cryoablation surveillance MR imaging shows increased nodular enhancement and an increase in lesion size confirmed tumor recurrence.

16 RADIOFREQUENCY ABLATION Ablative Technique and Imaging Guidance For heat based thermal ablation techniques such as RFA or MW, intraprocedural ablation findings are similar but vary slightly with the type of device and the relative speed of ablative change. RF and MW ablation is performed by placing one or more probes or within the renal tumor under US or CT guidance. Radiofrequency (RF) Ionic Agitation AC current Slow sustained heating >60 o C Coagulative Necrosis with Protein denaturation and cell death Raman et al. AJR 2000 Central Coagulative necrosis with hyperemic margin 15G single needle systems with expandable umbrella- like internal tines 17G internally cooled needles electrodes

17 MICROWAVE ABLATION Ablative Technique and Imaging Guidance Microwave (MW) Wavelike electromagnetic properties Rapid heating >100 o C Coagulative necrosis Available Microwave Devices: 2015 NeuWave: 2.45GHz Covidien: 2.54 GHz BSD Medical: 915 MHz Amica: 2.45 GHz Medwaves: MHz Microsulis: 2.45 GHz

18 RF and MICROWAVE ABLATION Intraprocedural Image Findings ULTRASOUND: Ultrasound shows antennae placement within the lesion targeted for microwave ablation (a). Temperatures inside the lesion raise above 50 degrees Celsius, water vapor and nitrogen are released as gas, resulting in echogenic reflectors (b) and eventually an echogenic cloud which fully encompasses the lesion (c,d). a b c d

19 RF and MICROWAVE ABLATION Intraprocedural Image Findings CT MONITORING: Unenhanced: Stranding Gas from vaporization Ablated lesion becomes smaller and of higher density Small subcapsular or perinephric hematomas Latrogenic perinephric or peritoneal low density fluid from percutaneous hydrodissection Enhanced CT: Complete lack of enhancement in the ablated lesion and a surrounding rim Lesion may appear larger Variable enhancement in surrounding unablated renal parenchyma May see a perilesional halo from ablation of perinephric fat MR MONITORING: On MR Imaging, the lesion becomes more T2 hypointense and more T1 hyperintense as heating above 60 degrees Celsius occurs. Towards the end of ablation, the original lesions shrink

20 RF and MICROWAVE ABLATION Intraprocedural Image Findings a b c d In a 68 year old man, diagnostic MR shows a T1 contrast enhanced posterior lesion (a) and US image used for lesion targeting for RF ablation (b). On unenhanced CT (c) intraprocedural gas (CO2) at the end of RF ablation. Also noted is crescent shaped D5W hydrodissection in the posterior pararenal space. Immediate post procedural contrast enhanced CT (d) shows lack of enhancement in the ablated lesion and a wedge shaped margin consistent with coagulation necrosis and infarct.

21 RF and MICROWAVE ABLATION Image Findings Immediately After Ablation Some of the immediate peri-lesional changes seen following thermal ablation include: blood products (b) (compare pre- with post-contrast to differentiate degraded blood products from residual tumor enhancement) a post-ablation halo (c) a cortical wedge shaped infarct associated with or adjacent to the treated lesion and as a result of segmental arterial thrombosis in the treatment zone (c) the presence of perinephric stranding (c) Immediately following treatment (24 hours to one week), a circumferential high attenuating region corresponding to a marginal hyperemic inflammatory reaction to the damaged cells can be seen in the surrounding renal parenchyma causing the lesion to appear larger than the pre-treatment lesion (a compared to c) Pre-Tx a b c

22 RF and MICROWAVE ABLATION Image Findings Immediately After Ablation Contrast Enhanced Ultrasound (CEUS): Intravascular microbubble US contrast agents have been approved for diagnostic US imaging outside the United States, however many centers in the US use these agents off label. This enables much higher renal mass contrast relative to renal parenchymal background in real time over multiple contrast phases. CEUS is can be used in patients with renal insufficiency or with a contraindication to contrast. a In a 77 year old woman, diagnostic sagittal MR shows a T2 hyperintense lesion (a). b Diagnostic CEUS shows lesion enhancement (b) c Immediately following microwave ablation, no residual enhancement can be seen on contrast enhanced ultrasound (c) indicating ablative success.

23 RF and MICROWAVE ABLATION Successful Ablation and Surveillance Imaging Findings MRI is preferred for most patients due to its superior tissue contrast, lack of ionizing radiation, and minimal contrast requirement relative to CT However either modality is preferable to performing an unenhanced US, which is limited for detection of early recurrences. Over time, the central area of coagulative necrosis is replaced by fibrosis and scar tissue rather than resorbed, likely accounting for the presence of a persistent mass at follow-up imaging Pre 3 month 6 month 1 year a b c d In a 73 year old woman with clear cell RCC treated with RFA, diagnostic MR shows a T2 hyperintense lesion (a). Longitudinal follow-up MR imaging shows a persistent post-ablation defect with peri-ablation halo without a change in size at 3, 6, and 12 months (b-d).

24 RF and MICROWAVE ABLATION Successful Ablation and Surveillance Imaging Findings With heat based thermal ablative techniques, the hallmark of successful renal tumor ablation is lack of tumor enhancement and without an increase in lesion size 3 month 6 month 1 year a b b c c A 70 year old man with an exophytic posterior papillary RCC lesion treated with RF ablation. Longitudinal surveillance CT imaging acquired at 3 month post RF ablation shows stranding within the perinephric fat (a). A 6 month post RF ablation CT image (b) shows no significant decrease in size, no residual enhancement, and emergence of the perinephric halo. A 12 month post RF ablation CT image (c) shows no significant decrease in size and no residual enhancement, indicating ablative success.

25 RF and MICROWAVE ABLATION Signs of Recurrence Any nodular or linear enhancing tissue within the original lesion 2 year f/u US 2 year f/u MR T1 precontrast At 2 year longitudinal followup imaging, the hypoechoic region appeared hypointense relative to the ablation zone on pre-contrast T1 (d). Pre b d a A 57 year old man with a large posterior endophytic clear cell RCC treated with RF ablation (a). c 2 year f/u MR T2 At 2 year longitudinal followup imaging, the echogenic ablated lesion became partially hypoechoic on US (b) and the hypoechoic region appeared T2 hyperintense (c). e f 2 year f/u MR T1 postcontrast 2 year f/u MR subtraction The ablated lesion enhanced on T1-post contrast corticomedullary imaging (e). MR subtraction imaging (f) confirmed tumor recurrence.

26 IRREVERSIBLE ELECTROPORATION (IRE) Ablative Technique and Imaging Role in tissue ablation is largely investigational Multiple needle electrodes deliver high voltage charges Malignant cell wall disruption and apoptosis Pech M. et al. Clinical Investigation 2011;34: A typical sonographic image obtained during monitoring of the positioning of the needle electrode for IRE. The hockey-stick curve shows the envelope of the kidney; the dark central mass is the tumor; and the slightly off-horizontal line passing through it is the electrode On ultrasound, there is a subtle decrease in US echotexture during electroporation On CT, aside from changes related to the needle, there are no reliable CT findings during the procedure Sometimes gas may be seen in the lesion due to mild associated thermal effects There are no MR compatible probes and thus intraprocedural MR findings have not been described Immediately following, there will be a relatively avascular hypodense poorly enhancing area corresponding to the elctroporated region with sharp margin parallel to the long axis of the needle

27 SUMMARY OF IMAGE FINDINGS AFTER ABLATION CRYOABLATION: Immediately after treatment: ablation zone appears larger than the original tumor In the first few days to months after treatment: emergence of the peripheral halo in perinephric fat surrounding the smaller high density ablated lesion Definition of successful ablation: no residual tumor enhancement and decrease in size, decreased stranding, hematomas & perinephric fluid Signs of recurrence: Enlarging ablation zone and increased linear or nodular enhancement >10HU RADIOFREQUENCY AND MICROWAVE ABLATION: Immediately after treatment: ablation zone appears larger than the original tumor In the first few days to months after treatment: emergence of the peripheral halo in perinephric fat surrounding the smaller high density ablated lesion Definition of successful ablation: no residual tumor enhancement and no change in lesion size, decreased stranding, hematomas & perinephric fluid Signs of recurrence: Enlarging ablation zone and increased linear or nodular enhancement >10HU IRREVERSIBLE ELECTORPORATION: Insufficient evidence as to length of time to renal tumor involution to occur after successful IRE ablation

28 LONGITUDINAL FOLLOW-UP IMAGING Unenhanced and multiphasic scans at three and six months following ablation to assess treatment success, followed by annual abdominal scans thereafter for five years. Beyond five years, there is no defined indication for imaging, but patients may undergo further scanning based on individual patient risk factors. Patients undergoing ablative procedures who have either biopsy proven low risk renal cell carcinoma, benign lesions such as oncocytoma, non-diagnostic biopsies or no prior biopsy, should undergo annual chest x-ray to assess for pulmonary metastases for five years

29 SUMMARY Proper imaging techniques are critical during ablation and in the assessment and management of RCC at longitudinal postablation follow-up. Surveillance imaging should be evaluated not only for tumor recurrence in the ablation zone, but also for evidence of metastatic disease and delayed complications.

30 REFERENCES 1. Higgins LJ, Hong K. Renal Ablation Techniques: State of the Art. AJR Am J Roentgenol Jul 23: Chodez M, Fiard G, Arnoux V, Descotes JL, Long JA. Ablative treatments in localised renal cancer: Literature review in Prog Urol Jul;25(9): Castro A Jr, Jenkins LC, Salas N, Lorber G, Leveillee RJ. Ablative therapies for small renal tumours. Nat Rev Urol May;10(5): Hinshaw JL, Lubner MG, Ziemlewicz TJ, Lee FT Jr, Brace CL. Percutaneous tumor ablation tools: microwave, radiofrequency, or cryoablation what should you use and why? Radiographics Sep-Oct;34(5): Finelli A, Rewcastle JC, Jewett MA. Cryotherapy and radiofrequency ablation: pathophysiologic basis and laboratory studies. Curr Opin Urol 2003; 13: Gunn AJ, Gervais DA. Percutaneous ablation of the small renal mass-techniques and outcomes. Semin Intervent Radiol Mar;31(1): Chodez M, Fiard G, Arnoux V, Descotes JL, Long JA. Ablative treatments in localized renal cancer: Literature review in Prog Urol Jul;25(9): Merkle EM, Nour SG, Lewin JS. MR imaging follow-up after percutaneous radiofrequency ablation of renal cell carcinoma: findings in 18 patients during first 6 months. Radiology 2005;235: Piscaglia F, Nolsøe C, Dietrich CF, et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall Med Feb;33(1): Goldberg SN, Grassi CJ, Cardella JF, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria. Radiology. 2005;235: Iannuccilli JD, Grand DJ, Dupuy DE, Mayo-Smith WW. Percutaneous ablation for small renal masses-imaging follow-up. Semin Intervent Radiol Mar; 31(1): Davenport MS, Caoili EM, Cohan RH, et al. MRI and CT characteristics of successfully ablated renal masses: Imaging surveillance after radiofrequency ablation. AJR Am J Roentgenol Jun;192(6): Breen DJ, Lencioni R. Image-guided ablation of primary liver and renal tumours. Nat Rev Clin Oncol 2015; 12: Wile GE, Leyendecker JR, Krehbiel KA, Dyer RB, Zagoria RJ. CT and MR imaging after imaging-guided thermal ablation of renal neoplasms. RadioGraphics 2007; 27: Thank you for taking the time to view our exhibit. If you have any questions or comments, please feel free to Heidi Coy at hcoy@mednet.ucla.edu.

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