Neurosurgical Use of Interstitial Laser Therapy (ILT)

The goal is to evaluate the use of minimally invasive interstitial laser therapy (ILT) in
the brain. Our group is in a unique position to offer image-guided ILT because of our
expertise and resources here at Brigham & Women's Hospital in the Departments of
Neurosurgery and Radiology. The therapy will be monitored and controlled by the use of
magnetic resonance imaging (MRI). ILT is a minimally invasive procedure in which the
targeted tissue is thermally destroyed in situ in a controlled fashion. The intra-operative
MRI provides a way to "see" the treatment. It can be used to treat disease by guiding
surgery by providing images of tissue changes during therapy.

In spite of its appeal as a minimally invasive technique, MRI-guided ILT is not commonly
practiced in the United States. One reason is that proper clinical implementation of ILT
requires an operating room (OR) setting and an MRI scanner - a very rare combination. Our
MRI-OR suite includes a sterile procedure room with a 0.5 Tesla vertically "open" magnet. In
the past, we have performed MRI-guided ILT procedures in 9 patients. While few in number,
this is the most extensive U.S. experience in ILT in the brain.

We have recently created a new image networking and display package for the visualization of
3D information during laser therapy. This provides a view of multiple image planes taken
through the tissue volume around the fiber tip from which the light emits. Recent FDA
approval for a "diffusing tip" laser and its associated catheter, provides us with an added
tool for the procedure. This diffusing technology had been available in Europe for clinical
use for years; however, there had been no FDA-approved device in the US until now. The
catheter is important because it protects the fiber; it is placed into the tumor first under
MRI guidance. Then the laser fiber inserted into the catheter to deliver the light. All
equipment used in this protocol is now FDA approved.

Each patient will undergo ILT. The procedure will be performed under anesthesia as per
standard procedures. The surgical placement of the laser fiber is a procedure identical to
the well-developed and practiced technique of brain biopsy. A hole approximately 1 cm in
diameter will be drilled in the skull through which the laser fiber will be placed under
image guidance to confirm the actual progress during the advance of the fiber. We will
deliver energy at a rate and distribution of 1-12 watts/cm for exposures less than 20
minutes. After the laser has been turned off, and the tissue cooled, MRI will show the
region of ablation. As needed, the laser fiber will be moved/re-located to assure that the
total target has been ablated. After the treatment is complete, the fiber is withdrawn,
final images are acquired and the surgical site is closed and dressed. On the day after the
procedure, the patient will undergo a 24 hour follow-up MRI exam. There will be
post-operative care as with any neurosurgical patient.

The following continuous variables will be measured in this study:

- The pre-operative tumor volume (VO) in cc

- The post-operative ablated volume (V1) in cc

- The intra-operative critical temperature volume (VT) in cc

- The intra-operative critical dose volume (VD) in cc

The following statistical hypothesis tests will be conducted.

Statistical Hypothesis 1. A tumor can be completely ablated by ILT with MRI-guidance.

We propose that the difference between the mean pre-op tumor volumes and the post-op ablated
volumes (VO and V1, respectively) is zero. Residual tumor is defined as (V0-V1). This will
be determined by calculating the mean of the values of the proportion of residual tumor,
defined as (V0-V1)/ V0. Use of the proportion normalizes the data for different sized
tumors.

Statistical Hypothesis 2. The MRI-based 3-D temperature map of the tissue during ILT is
predictive of destruction.

We propose that the difference between the mean post-op ablated volumes and the
intra-operative critical temperature volumes (VT and V1, respectively) is zero. This will be
determined by calculating the mean of the values of the proportion of the difference between
them, defined as (VT-V1)/VT.

Statistical Hypothesis 3. The thermal dose map is predictive of tissue destruction.

We propose that the difference between the mean post-op ablated volumes and the
intra-operative critical dose volumes (VD and V1, respectively) is zero. This will be
determined by calculating the mean of the values of the proportion of the difference between
them, defined as (VD-V1 /VD).

Also, data will be collected through Neurological Examinations.

Inclusion Criteria:

- Male or female

- Age 18+

- Surgically difficult to access tumors including intracerebral metastases

Exclusion Criteria:

- Patients unwilling or unable to give written consent

- Patients at risk for cardiac ischemia

- Patients who cannot physically fit in the MRI scanner in the MRI OR

- Patients with contraindications to MRI imaging such as pacemakers, non-compatible
aneurysm clips, shrapnel, and other internal ferromagnetic objects

- Patients with coagulopathies, severe medical problems, cardiac arrhythmias or
abnormal BUN