The Cleveland Clinic Foundation

Picker International, Inc.

Gene H Barnett

Donald W Kormos

Iain H Kalfas

Charles P Steiner

David W Piraino

Christopher H Wood

Patrick A Dayton

Damir Janigro

Marc Mayberg

The present invention relates generally to a peripheral marker or marker of blood brain barrier integrity and methods of using them in the diagnosis, prognosis, and treatment of a variety of diseases. The preferred embodiments of the present invention relate to methods, compositions, kits, and assays useful in determining the integrity or permeability of a blood brain barrier. The various embodiments of the present invention can be used to identify subjects at risk for developing a disease associated with increased permeability of the blood brain barrier, as well as to provide insight on the ability of an agent or agents to pass the blood brain barrier. Preferably, increased levels of S100&#x3b2; protein are used alone or in combination with other markers of diseased state in order to diagnose and prognosticate permeability of the BBB.

Peripheral marker of blood brain barrier permeability

A patient is secured to a subject support ( ). A stereotaxic wand ( ) is inserted into a tool guide ( ). The wand has a tip portion ( ), a portion extending along a pointing axis ( ) of the wand, an offset portion ( ) which is offset from the pointing axis of the wand, and at least two wand emitters ( ), mounted in alignment with the pointing axis of the wand. The two emitters selectively emit wand signals which are received by three receivers ( ) mounted to a frame assembly ( ). The tool guide includes a bore ( ) extending along a guide axis. The bore is configured for selectively receiving a tool and the tip portion of the wand. An entry point and a trajectory are identified by the surgeon with the wand in the guide. More specifically, a trajectory and location of the wand are superimposed on a diagnostic image on a monitor ( ). If the surgeon is satisfied with the entry point and trajectory shown on the monitor, a surgical tool is inserted into the bore while the tool guide is held along the designated trajectory and at the designated entry point.

Tool guide for a surgical tool

A fiducial positioning cup (86) has a hemispherical well (92) in its top and a central bore (94) from a bottom of the hemispherical well (92) to a base of the positioning cup (86). The fiducial cup (86) is then attached to the skin (88) of a patient. A needle (110) is passed through the fiducial positioning cup (86) to mark an area of the patient's skin (88) with a tattoo (112). Fiducials (84) are secured in the fiducial positioning cups (86). Magnetic resonance or other diagnostic images are taken. Once the images are taken, the fiducials (84) and fiducial positioning cups (86) are removed. The tattoo mark (112) remains. The fiducial positioning cups (86) are reattached when a stereotactic procedure is to be performed. The needle (110) is passed through the fiducial cups (86) and a tip of the needle (110) is aligned with the tattooed mark (112) on the patient's skin (88). The fiducial cup (86) is then lowered and centered over the tattooed mark (112). A stereotactic wand (36) is aligned with the magnetic resonance image by placing a tip (42) of the wand (36) in the fiducial cups (86) and emitting signals. The stereotactic system decodes the signals to identify where the tip (42) of the wand (36) is on the magnetic resonance image.

Fiducial positioning cup

A position signaling is usable in connection with an image guided surgery system. A plurality of infrared emitters are mounted on a reference object. The reference object is in turn attached to the rocker arm of a head clamp. The head clamp includes a frame and a first head engaging pin secured to one side of the frame. The rocker arm includes two head engaging pins and is movable in relation to the frame. The image guided surgery system uses the signals provided by the infrared emitters to determine and account for movement of the patient's head.

Apparatus for anatomical tracking

An interventionalist or operator uses a variety of apparatus 30 including tools, tool guides, and pointers in a procedure on a region of interest. The region of interest was previously the subject of a diagnostic imaging procedure to generate three dimensional diagnostic image data, selective slices or other portions of which are displayable on video monitors 34. The position of the apparatus 30 in operator space is determined by actuating emitters 32, receiving the emitted signals with receivers 12, and calculating the position of the pointer in operator space. A pair of radio translucent constructions 14, 16 each carry a plurality of radiopaque markers 18 which are positioned adjacent the region of interest. Two or more projection images are taken through the region of interest and the radiopaque markers using a movable x-ray tube 22 and radiation detector 24. The operator uses a control 36 to position cursors on corresponding anatomical markers in both the projection images and images from the diagnostic data to determine a correlation or transform between projection image space and diagnostic data space. The operator positions a tip of the pointer 30 on each of the radiopaque markers and actuates the emitters 32 to determine the position of the radiopaque markers in operator space, i.e. to correlate operator space with projection image space. In this manner, the correlation or transform between operator space and diagnostic data space is generated through the intermediary of projection image space.

Non-invasive spine and bone registration for frameless stereotaxy

A surgical guide for use with an image guided surgery includes first and second surfaces. At least three signaling devices such as infrared emitters are disposed on the first surface, and a cylindrical mounting boss is disposed on the second surface. A guide aperture is perpendicular to the first and second surfaces and extends between them. The guide aperture is configured to support a surgical tool such as a biopsy needle. A sleeve may be placed in the aperture to support additional tools.

Trackable guide block

A patient is secured to a subject support (10). A stereotaxic wand (40) is inserted into a tool guide (60). The wand has a tip portion (44), a portion extending along a pointing axis (46) of the wand, an offset portion (42) which is offset from the pointing axis of the wand, and at least two wand emitters (48, 50), mounted in alignment with the pointing axis of the wand. The two emitters selectively emit wand signals which are received by three receivers (14) mounted to a frame assembly (12). The tool guide includes a bore (66) extending along a guide axis. The bore is configured for selectively receiving a tool and the tip portion of the wand. An entry point and a trajectory are identified by the surgeon with the wand in the guide. More specifically, a trajectory and location of the wand are superimposed on a diagnostic image on a monitor (30). If the surgeon is satisfied with the entry point and trajectory shown on the monitor, a surgical tool is inserted into the bore while the tool guide is held along the designated trajectory and at the designated entry point.

Frameless stereotaxy system for indicating the position and axis of a

A patient is secured to a subject support (10). A stereotaxic wand (40) is inserted into a tool guide (60). The wand has a tip portion (44), a portion extending along a pointing axis (46) of the wand, an offset portion (42) which is offset from the pointing axis of the wand, and at least three wand emitters (48, 50, 52), mounted in alignment with the pointing axis of the wand. The three emitters selectively emit infrared light which is received by two CCD cameras (14) mounted to a frame assembly (12). The tool guide includes a bore (76) extending along a guide axis. The bore is configured for selectively receiving a tool and the tip portion of the wand. An entry point and a trajectory are identified by the surgeon with the wand in the guide. More specifically, a trajectory and location of the wand are superimposed on a diagnostic image on a monitor (30). If the surgeon is satisfied with the entry point and trajectory shown on the monitor, a surgical tool is inserted into the bore while the tool guide is held along the designated trajectory and at the designated entry point.

Stereotaxy wand and tool guide

A patient's head is anchored (16) at one end of a patient support (10). An array of receivers (50) are mounted on a frame (12) which is fixed to the patient support. The frame carries at least one reference transmitter (52). A wand (42) has at least two emitters (44, 46) mounted thereto. By measuring relative travel time of the signals from the wand emitters to the receiver array and comparing the travel time with travel time over a known distance from the reference transmitter to one or more of the receivers, the position of the wand in a coordinate system of the patient support is determined (80). A three-dimensional array of diagnostic image data was taken through the anchored portion of the patient and at least three markers (114) affixed to the patient. By positioning the wand on the markers after the patient is secured to the patient support, a transform (110) between the patient support coordinate system and the image data coordinate system is derived. Once the relationship between the coordinate systems is known, the surgeon can use the wand to select locations and orientations on a surface of the patient and retrieve corresponding portions of the image data for display on video monitors (30).

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Gates Mills, OH, United States of America

Gene H Barnett