Novel Therapy of Acute Ischemic Stroke Using Selective Endovascular Brain Cooling Under MR Guidance

Lay Summary

Testing a Novel Method for Protecting the Brain after Stroke: Intra-Arterial Cooling

Researchers plan to test whether directly cooling the area of the brain that is at risk of further damage following a stroke, can provide protection against injury. The brain area would be cooled by injecting a cold solution through the artery supplying that brain area. If this approach is effective, it could substantially reduce stroke-induced functional disabilities in patients.

One of the few successful ways of protecting the brain after an injury from a stroke, cardiac arrest, or trauma, is to cool the body (including the brain) down from the normal 37 C to temperatures in the 25 to 30 degree range. This cooling protects the brain by slowing down its metabolism. The slowed metabolic rate reduces the brain’s demand for oxygen and other nutrients, and also slows biochemical reactions that would otherwise further damage the injured brain. Called “hypothermia,” cooling is also used prophylactically to protect the brain in situations in which it is at risk of being injured, such as during cardiac surgery. Lowering the temperature of the whole body to cool the brain takes time to achieve, however, and usually requires sedation, if not anesthesia, to prevent shivering and intolerance by the patient.

To create a faster, more feasible and targeted cooling of brain areas surrounding an injury, or at risk of injury, an experienced team of investigators at Columbia will create hypothermia in a different way. They will directly cool the brain areas at risk by injecting a cold solution through the brain artery serving the vulnerable brain area. As is common practice in the acute treatment of stroke, the investigators will first perform an angiogram in patients who develop acute stroke and are entered into the study.  By injecting a dye into arteries that lead to the brain, clinicians determine exactly which artery may be blocked and limiting blood flow to the brain, producing the stroke.

Using these same methods, the investigators then will inject a bolus of cold solution into the arteries adjacent to the blocked artery to cool the surrounding brain tissue at risk. The result will be that only the damaged and at-risk areas of the brain will be cooled, and the rest of the body, including the rest of the brain, will stay at normal temperature. This will obviate any requirement for using sedation or anesthesia.

There are two other components of this clinical treatment approach. First, the investigators are also developing MRI-based imaging methods to determine the internal temperatures of the brain. This will allow them to substantiate whether their experimental selective cooling technique is actually taking place. In addition, they will merge the diagnostic and therapeutic steps for stroke, by interspersing the cooling solution with the dye that is used in the angiogram to identify the blocked artery. Through this combined process, they will diagnose and treat the affected brain areas concurrently.

Abstract

Novel Therapy of Acute Ischemic Stroke Using Selective Endovascular Brain Cooling Under MR Guidance

The goal of this study is to develop a fast intra-arterial method of cooling the brain, and a non-invasive technique for monitoring brain temperature in humans. Therapeutic hypothermia is an effective neuroprotection method that has been applied in humans (cardiac surgery, neonatal asphyxia, and out-of-hospital cardiac arrest). However, the slow cooling rate and systemic effects of conventional cooling methods limited them from being an effective therapy for ischemic stroke.

The objective of the study is to cool the brain quickly, selectively and safely through arterial infusions of cold saline, with minimal effect on the rest of the body. The research team will investigate how temperatures change in the brain and body during selective brain cooling; the effect of local brain cooling on brain metabolism, cerebral blood flow (CBF), other physiological parameters and vital functions; and whether mild local brain cooling (33° to 35°C) affects neuropsychological functions. These questions may potentially be addressed by non-invasive MR thermometry and CBF measurement using cold saline as a contrast medium. MR thermometry will be used to map brain temperature of healthy subjects and will be validated by MR spectroscopic measurements of absolute brain temperature on patients with known body temperature deviations.

The research team will assess the feasibility of using cold i.v. bolus as a contrast-enhancing substance to measure CBF and to compare this method with arterial spin labeling (ASL) and gadolinium contrast-enhanced imaging. Data obtained from the clinical studies will be integrated into an existing mathematical model of brain temperature response to intra-arterial cold saline infusion.

The results of this project will increase our knowledge of the physiology of the human brain under local hypothermia, and serve as a foundation for a novel treatment approach for acute ischemic stroke using intra-arterial brain cooling in the MR environment.