Preclinical cerebral cryoablation in non-tumor bearing pigs

Abstract

Patients with brain metastases, the most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed. Cryoablation is a minimally invasive, well-tolerated, and effective procedure commonly applied for treatment of renal tumors and certain other malignancies. We aimed to examine the clinical usefulness of this procedure in a step-by-step program starting with cerebral cryoablation in healthy pigs. In four terminal and four non-terminal non-tumor bearing pigs, we studied immediate and delayed effects of cerebral cryoablation. Safety was assessed by computed tomography (CT), and clinical observation of behavior, neurological deficits, and wellbeing. Effects were assessed by histological and immuno-histochemical analyses addressing structural and metabolic changes supported by additional magnetic resonance imaging (MRI) and positron emission tomography (PET) in the non-terminal animals. Using CT-guidance, cryoablation probes were successfully inserted without complications, and ice formation could be monitored real-time with CT. No animal developed neurological deficits or signs of discomfort. Histological and immunohistochemical analyses, MRI, and PET revealed profound structural and biological damage within the lesion. MRI and PET revealed no long-term damage to healthy tissue outside the cryoablation zone. Cerebral cryoablation appears to be a feasible, safe, and controllable procedure that can be monitored successfully with CT. The net effect is a dead brain lesion without damage of either nearby or remote healthy structures. Immediate changes are local hemorrhage and edema; delayed effects are perfusion defects, immune system activation, and astrogliosis.

Manufacturing of Sapphire Crystals with Variable Shapes for Cryosurgical Applications

“…Particularly, it ensures higher rate of tissue freezing, higher ice-ball volume and lower temperatures. Finally, such applicators can be additionally assisted with optical monitoring [8], which allows to overcome one of the main problem of cryosurgery, that is the uncontrollable tissue damage [36,43,44].…”

Optical Sensing of Tissue Freezing Depth by Sapphire Cryo-Applicator and Steady-State Diffuse Reflectance Analysis

“…The evident drawback of this approach is the absence of real-time monitoring of tissue freezing. Therefore, it is desirable to use other techniques for monitoring, such as ultrasound (US) [ 19 , 20 ] and magnetic resonance imaging (MRI) [ 21 , 22 , 23 ], computed tomography (CT) [ 24 , 25 ] and temperature measurements [ 26 ]. Visualization by US, CT and MRI requires additional sensors or even expensive systems that can not be combined with the cryosurgical instrument.…”

Feasibility test of a sapphire cryoprobe with optical monitoring of tissue freezing

“…To achieve the cell death, the tissue should be rapidly cooled down to the temperatures below the threshold that lies between À20 C and À40 C and thawed slowly after that. Repetition of the freezing cycle increases the freezing volume [16]. The required cooling rate is guaranteed by using special cryoprobes, which have undergone significant changes since the introduction of the first instruments for tissue freezing [17,18].…”

“…The process of tissue freezing requires continuous monitoring of the ice ball volume during cryoprobe application, aimed at complete freezing of the region of interest and preventing the damage of healthy adjacent tissues. Various approaches are applied for this purpose, including visualization by ultrasound (US) [21,28,29], magnetic resonance imaging (MRI) [30][31][32], computed tomography (CT) [16,[33][34][35], and temperature measurements [36,37]. While MRI and CT remain expensive and are quite hard to be integrated into surgical workflow, US is more available, but less accurate and needs additional US-sensor placed aside to the cryoprobe.…”