III. Cell destruction by freezing and cryoprobe development

Size: px

Start display at page:

Download "III. Cell destruction by freezing and cryoprobe development"

Corey Dalton
7 years ago
Views:

1 III. Cell destruction by freezing and cryoprobe development 1

2 WHAT IS CRYOSURGERY? Cryoprobe Surface iceball formation Ice-ball Cryoprobe Cryosurgery of liver (Angular insertion) Cryosurgery of liver (Vertical insertion) Multi-probes cryosurgery of irregularly shaped large tumour Cryosurgery, sometimes referred to as cryotherapy or cryoablation, is a surgical technique that employs freezing at cryogenic temperatures to destroy undesirable tumour cells. It is effected by means of cryoprobe(s) either by placing its continuously cooled tip on or into the tissues to be destroyed 2

3 ADVANTAGES OF CRYOSURGERY Effective Well controlled Little post-surgical effects Preserves adjacent tissues by localizing cell destruction Repeatable Can be guided using Ultra-Sound Imaging and MRI 3

4 CRYOSURGERY FREEZING PARAMETERS Rate of freeze Duration of freeze Rate of warming or thawing Duration of thawing Number of thawing cycles Number of probes Placement of probes 4

5 CELL DESTRUCTION MECHANISMS DURING CRYOSUGERY Mechanisms of Cell Destruction Immediate Cell Destruction Delayed Cell Destruction Vascular Stasis (cell death due to restriction of blood flow) Cell Destruction by Cooling Cell Destruction by Freezing Hypothermia Extracellular Ice Crystallisation Intracellular Ice Crystallisation Lethal Temperature (-20 to -50 ºC) 5

6 Extracellular Ice Crystallisation Change in concentration gradient Formation of hypertonic extracellular environment Movement of water out of cell through osmosis Cells shrink leading to damage in membranes and constituents Movement of solutes into cell when concentration within cells reaches certain intensity 6

7 Intracellular Ice Crystallization High cooling rate hinders osmosis Ice crystals form within cells to maintain equilibrium Thermodynamically super cooled and unstable Cell membrane ruptures irreversibly due to volume expansion Functions of organelles interrupted 7

8 Lethal Temperature Temperature - Most common indicator of cell death Cells differ in susceptibility to freezing injury over a range of -5 C C to -50 C Temperature to ensure total lethality of cancerous cells is -50 C 8

9 Cooling Rate vs Cell Destruction Lower or Rapid cooling rate results in reduced cell survival rate Slow cooling Intermediate cooling Rapid cooling Optimal cooling rate for maximum cell survival Survival signature is cell species dependent Function of multiple parameters eg.. membrane permeability 9

10 CRYOSURGERY RESEARCH AREAS DEVELOPMENT OF THERMAL PROCESS MODEL FOR STUDY OF CRYOSURGERY PERFORMANCE STUDY OF CRYOPROBES FOR CRYOSUGERY PRINCIPAL RESEARCH OBJECTIVES To build an accurate thermal model for temperature distribution calculations in order to study various protocol parameters to maximize the destruction of tumorous tissue within a defined spatial domain. To study the efficacy of different cryoprobe s performance in terms of physical dimensions, shape and number of probes employed in administrating cell destruction within tumorous tissues. 10

11 METHODOLOGY Formulate a detailed bio-heat model to study the rate of cell destruction within a liver tumor undergoing cryosurgery. Validate model with in-vivo and in-vitro experimental data. Employ the calibrated model to study the effects of different freezing rates, freeze/thaw cycle(s), and multi-probe freezing on the overall cellular damage within a liver tumor. Model outputs include spatial temperature profiles, isotherms, freezing and thawing rates, ice-ball position and degree of cell destruction 11

12 Cell survival for different cryoprobes diameter 100 Cell Survival Vs Distance from Probe Centre (radial) 90 Tumour radius (7.5mm) Healthy Tissue Region mm Probe 5mm Probe 8mm Probe Cell Survival (%) mm Probe radial longitudinal 5mm Probe 3mm Probe Area under graph shows cell survival due to cooling rate after a certain period of time Distance (mm) Standard protocols call for an additional buffer freezing region of 10mm from the edge of tumor. Maximizing cell survival in this healthy tissue region is desired. Results show that higher percentages of cell survival of 37% and 6% occurred for 8mm and 5mm probes, respectively. 12

13 Variation of Number of Freeze/Thaw Cycles Cell survival vs Distance from center of 3mm probe (radial) 100 Region affected by 1st freeze/ thaw cycle No freeze/thaw cycle 90 1 freeze/thaw cycle freeze/thaw cycle Tumor size = 30mm No freeze/thaw cycle Region affected by 2nd freeze/ thaw cycle Cell Survival (%) Region of permanent cell death due to lethal temperature of -50 C Region affected by cooling rate only 2 freeze/thaw cycle 1 freeze/thaw cycle Distance (mm) The implementation of freeze/thaw cycle enhances tumorous cell destruction. Increased number of freeze/thaw cycles provided additional 13 cell destruction quality by as much as 20%.

14 Variation of Number of Freeze/Thaw Cycles The advantages of implementing higher number of Freeze/Thaw cycles may be attributed to following: Additional deleterious physiochemical changes Higher probability of lethal intracellular ice formation Boundary of cell destruction moved towards tumour edge Disadvantage: Longer surgical process Optimal number of Freeze/Thaw Cycle exists! 14

15 Multi-probes cryosurgical process Cell Survival vs Distance (radial) Region affected by lethal temperature of -50 degree celsius Tumor size = 45mm Single 8mm probe Region affected by cooling rate Single 8mm probe Cell Survival (%) Two 5mm probes Three 3mm probes radial Two 5mm probes 30 Three 3mm probes longitudinal Distance (mm) Employing a three probe arrays can improve freezing damage by as much as 19% to the targeted tumour tissue while minimizing the collateral damage to healthy normal tissue. 15

16 FUTURE DIRECTIONS Optimization treatment planning of multiprobe cryosurgery to determine cryoprobes placement for maximizing the efficacy of freezing protocols. Further studies on different freezing and thawing programs for different multi-probe arrays to administer maximum cell destruction effect on tumour tissues. To design smart miniaturized cryoprobes whereby the cooling parameters can be precisely controlled based on biological feedback information such as maximum cell destruction rate, size and shape of the tumour. Studies on the design of specially shaped cryoprobe tips to cater for irregularly shaped tumours and tumours located on hard to excess regions. 16

A PATIENT S GUIDE TO ABLATION THERAPY

A PATIENT S GUIDE TO ABLATION THERAPY THE DIVISION OF VASCULAR/INTERVENTIONAL RADIOLOGY THE ROBERT WOOD JOHNSON UNIVERSITY HOSPITAL Treatment options for patients with cancer continue to expand, providing