MXPA97006545A - Device for loading and centering a vascular radiation therapy source - Google Patents

Abstract

An intravascular catheter (10) having an expandable inflation region (12) adapted for centering a radiation dose in a body lumen for a period of time sufficient to permit delivery of a radiation dose to the body lumen. The catheter includes a delivery lumen (26), and a blind internal lumen (30) for receiving a wire (36) having a radiation source (38) located at the distal end of the wire. The blind internal lumen is received in the delivery lumen of the catheter. The blind internal lumen prevents contamination of the radiation source by fluids from the body lumen. The radiation source is advanced through the blind internal lumen towards the inflation region of the catheter. The inflation region includes a plurality of balloon lobes (14, 16, 18) at the distal end of the catheter. The plurality of balloon lobes, when inflated, can center the radiation source within a curved section of the body lumen.

Description

DEVICE FOR LOADING AND CENTERING A SOURCE OF VASCULAR RADIATION THERAPY. BACKGROUND OF THE INVENTION. This invention is generally related to intravascular catheters, suitable for maintaining the opening of a body lumen during the delivery of a radiation source to the body lumen. In typical percutaneous transluminal coronary angioplasty procedures (PTCA = percutaneous transluminal coronary angioplasty), a guiding catheter having a preformed distal tip is inserted percutaneously into a patient's cardiovascular system through the brachial or femoral arteries and advanced there until its distal tip east in the ostium (opening or hole) of the desired coronary artery. A guidewire and a dilatation catheter having an inflatable balloon at its distal end is inserted through the guide catheter with the guidewire slidably disposed within an inner lumen of the dilatation catheter. The guide wire is first advanced from the distal end of the guide catheter and then maneuvered to the coronary vasculature of the patient having the lesion to dilate, and then advanced beyond the lesion. Subsequently, the dilatation catheter is advanced over the guidewire until the dilatation balloon is located through the lesion. Once in position through the injury, the balloon of the dilatation catheter is filled with radiopaque liquid at relatively high pressures (eg, greater than about 1013 x 105 Pa (atmospheres)) and inflated to a predetermined size (preferably the same as the internal diameter of the artery at that site) to radially compress the atherosclerotic plaque of the lesion against the inside of the wall of the artery, in order to dilate the lumen of the artery. The balloon then deflates in such a way that the dilatation catheter can be removed and the blood flow through the dilated artery resumed. After an angioplasty procedure, restenosis occurs at or near the site of the original stenosis in the artery, occasionally. The smooth muscle cells of the artery can proliferate at the site of the angioplasty treatment. Restenosis may result in a reformation of the lesion and a narrowing of the artery at the site. Various devices and methods have been developed to prevent restenosis, including the use of an expandable stent at the distal end of the catheter designed for long-term implantation in the body lumen. Other devices and methods to prevent restenosis after angioplasty or other arterial intervention procedure employ a source of radiation delivered through a balloon. The radiation operates to destroy the proliferating cells, thus preventing the development of restenosis.

There is a need in the art for a catheter with a minimal profile having an expandable region, which can maintain the opening of an artery and allow a source of radiation to be delivered to the treatment area for a sufficient period of time to prevent development of restenosis. This intravascular catheter should be easy and inexpensive to manufacture, has an expandable region that is strong and reliable under pressure and is capable of forming a variety of structures to allow flexibility in the amount and pattern of expansion and deformation of the expandable region. In addition, the associated radiation source should be protected from any contact with the patient's bodily fluids, in order to allow the radiation source to be reused. The present invention meets these needs. SUMMARY OF THE INVENTION The invention is directed to an intravascular catheter with an expandable balloon located at the distal end of the catheter body that can maintain an open body lumen for a period of time sufficient to allow delivery of a radiation source to a body lumen. , while allowing blood perfusion. In one embodiment the catheter comprises a catheter body having a proximal end and a distal end; an inflation region positioned at the distal end of the catheter body, the inflation region has at least two lobes, wherein the lobes are adapted to contact the body lumen when the lobes are inflated; and the catheter body further includes an internal lumen extending from the proximal end of the catheter body and adapted to receive a radiation source wire at the proximal end for delivery to the inflation region; wherein the inflation of the lobes in the region of central inflation the wire source of radiation within the body lumen. A method for maintaining the opening of a body lumen and delivering radiation to the body lumen, comprises the steps of introducing a catheter having a proximal end and a distal end to a treatment site in the body lumen; dilate an inflation region disposed at the distal end of the catheter, the inflation region has at least two lobes; charging a radiation source wire having a radiation source at the distal end of the radiation source wire in an internal lumen in the catheter; advancing the distal end of the radiation source wire to the inflation region, such that the radiation source is centered within the body lumen and substantially equal amounts of radiation energy are directed to the body lumen, while the region is dilated of inflation; and maintaining the source of radiation in the inflation region, for an adequate time to deliver a therapeutically significant dose of radiation to the treatment site.

In one aspect of a catheter embodiment, multiple balloons are inflated to center the source of radiation within the body lumen, especially when the body lumen is curved. In another aspect of one embodiment of the invention, the internal lumen of the catheter is a blind lumen having a distal end that is not open to the body. The radiation source is delivered through the blind lumen in order to avoid contamination of the radiation source during treatment. In another aspect of one embodiment of the invention, the catheter includes a delivery lumen adapted to receive either a guide wire or the blind internal lumen. The catheter body should have a small minimum profile. In another aspect of one embodiment of the invention, the catheter further includes perfusion ports to allow blood flow while the balloons are inflated. These and other aspects of the invention will be more apparent from the following detailed description, in conjunction with the accompanying exemplary drawings. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is an elevation view, partly in cross section of an intravascular catheter incorporating characteristics of the present invention. Figure 2 is a cross-sectional view of the catheter of Figure 1 taken on lines 2-2.

Figure 3 is a cross-sectional view of the catheter with radiation source wire loaded in the inner lumen and the lobes of multiple balloons of the catheter are inflated within a curved section of an artery to center the radiation source wire. Figure 4 is a flow chart describing the steps in a method for charging and centering the radiation source in a catheter according to the present invention. Figure 5 is an elevation view of an embodiment of an intravascular catheter illustrating the first step of Figure 4 according to the present invention. Figure 6 is an elevational view of the catheter of Figure 5, illustrating the second stage of Figure 4 according to the present invention. Figure 7 is an elevation view of the catheter of the Figure 5, which illustrates the third stage of Figure 4 according to the present invention. Figure 8 is an elevational view of the catheter of Figure 5, illustrating the fourth stage of Figure 4 according to the present invention. Figure 9 is an elevational view of the catheter of Figure 5, illustrating the fifth step of Figure 4 according to the present invention.

Figure 10 is an elevational view of the catheter of Figure 5, illustrating the sixth stage of Figure 4 according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED MODALITIES The present invention provides a catheter that is adapted to deliver a source of low dose radiation to a body lumen, such as a coronary artery, for a prolonged period of time. The catheter allows blood perfusion during radiation therapy and to center the radiation source in such a way that equal amounts of radiation are applied to the artery. While the catheter is described in detail as applied to the coronary arteries, those skilled in the art will appreciate that the catheter can be used in other body lumens alike, including peripheral arteries and veins. When different modalities have similar elements, identical reference numbers have been used. One embodiment of intravascular catheter 10, as illustrated in Figure 1, includes an elongate catheter body 11, and an expandable or expandable inflation region 12 in the distal state of the catheter body. The inflation region 12 can be constructed of a single balloon, multiple lobes, or individual balloons. The inflation region 12 includes a first balloon lobe 14, a second balloon lobe 16 and a third balloon lobe 18 arranged adjacent to each other. Globe lobes can be elastic or inelastic. When the globe lobes are inelastic, the lobes of preference inflate approximately the same diameter. The balloon lobes are preferably spaced apart by relatively non-inflatable or non-expandable regions. 19. Multi-balloon catheters are described in U.S. Pat. 5,002,532 and 5,415,625. The lobes of balloon 14, 16 and 18 may be individual balloons that are separately inflatable or the lobes may be part of a simple multi-lobed balloon. The lobes can be inflated by a single inflation lumen 20 or by multiple individual inflation lumens. Once the catheter assembly is properly positioned at the treatment site in the patient's vasculature, the balloon lobes in the inflation region are inflated. The triple lobe balloon configuration allows the distal end of the catheter body to remain on a select axis relative to the artery even when the artery is curved. The catheter further includes a delivery lumen 26 that extends through the body of the catheter 11. The catheter assembly 10 can be delivered to a treatment site on a guidewire 28 through the delivery lumen. The guide wire 28 includes a core member and a helical coil or other flexible body disposed relative to and fixed to the distal portion of the core member. A rounded plug of radiopaque material is typically provided at the distal tip of the coil.

Perfusion ports 22 are formed at the distal end of the catheter body in order to allow blood flow into the artery while the balloon lobes are inflated. Blood enters the perfusion orifices 22 leading to the delivery lumen 26 and blood is transported back and through the delivery lumen. Blood entering the perfusion ports 22 on one side of the inflation region passes down the delivery lumen 26 over the guidewire and exits the catheter through the distal end of the delivery lumen. Additional perfusion ports 22 can be formed in the catheter body at the opposite end of the inflation region to allow blood to exit the delivery lumen 26. Perfusion ports are formed in the side wall of the catheter body and can be cut in the notch shape. Perfusion dilatation catheters are described in US Patents. Nos. 4,790,315 and 5,334,154. The catheter assembly can be formed from conventional construction materials. The material forming the catheter body can be any metal or polymer with ductile properties that would be acceptable for the needs of intravascular devices. Specifically, the selected material for the catheter body should have sufficient flexibility to advance and navigate easily through a tortuous anatomy.

The dimensions of the catheter assembly 10 can be the same dimensions as for the vascular catheters used in angioplasty procedures. In the mode for use in the peripheral arteries, the total length of the catheter assembly is approximately 100 to 175 centimeters (cm) and the operative length of the catheter body is preferably 125 cm. The outer diameter of the catheter body is preferably 2.21 millimeters (mm). The diameter of the catheter body is in the range from about 0.02 to 0.152 cm. The balloon lobes of the inflation region in the non-inflated condition have approximately the same diameter as the catheter body. The balloon lobes are preferably inflated to a diameter of about 5 mm. Each balloon lobe preferably includes a substantially flat region that has an approximate length of 1.5 cm when inflated. The inflation region 12 occupies approximately 10 cm on the distal end of the catheter body. The diameter of the delivery lumen 26 should be larger than the diameter of the guide wire 28 to allow the catheter to be easily advanced and removed over the guidewire. In addition, the supply lumen diameter 26 should be dimensioned close to the diameter of the internal lumen 30 which is inserted into the supply lumen after the guide wire 28 is removed. The internal lumen preferably has a length of approximately 130 cm, an inner diameter of 1.37 mm and an outer diameter of 1.22 mm. The radiation source wire and the guide wire preferably have a diameter of approximately 1.1 mm, although the radiation source wire and the guide wire do not need to have the same diameter. It will be understood that the catheter assembly 10 can be constructed to have the dimensions and flexibility suitable for use and placement in other arteries including the coronary artery. As illustrated in Figures 2 and 3, the catheter body includes the inflation lumen 20, the perfusion channels 22 and delivery lumen 26. The guide wire 28 occupies the delivery lumen 26 while the catheter is delivered to the site. of treatment. Once the catheter is in place, the guide wire 28 is removed and the internal lumen 30 is inserted into the delivery lumen 26. The internal lumen is preferably inserted into the catheter using a support mandrel removably inserted into the internal lumen 30 and pushing it distally to the supply lumen 26, the internal lumen 30 is a blind lumen lining (closed end) that closes at the distal end 32 to prevent entry of any bodily fluids such as blood into the internal lumen. The distal end of the internal lumen 30 is placed in the inflation region 12 of the catheter. After the support mandrel is removed, a radiation source wire 36 is charged to the blind internal lumen. The radiation source wire 36 is inserted into the blind lumen for a period of time to deliver the required radiation dose to the body lumen. The distal end of the radiation source wire 36 contains a radiation dose in the form of radiation nodes 38. The radiation source wire may alternatively contain radioactive gas, liquid or paste, or have a radioactive source coated at its distal end. Preferably, a low dose of radiation is delivered to the artery or vessel. It is preferred that a dose level of about .1 to 1.40 curies be employed. More preferably, a dose level of about 1.0 to 2.0 curies is delivered to a coronary artery for a sufficient time to provide from about 500 to about 3000 rads. The radiation nodes 38 can be placed at the appropriate location at the distant end of the radiation source wire 36 to deliver the radiation dose. Inflation of the triple lobe balloon centers the radiation source wire 36 and more specifically the radiation nodes 38 within the artery, such that uniform and equal amounts of radiation are applied to the artery wall during treatment. Centering the radiation source wire 36 on the artery can prevent non-uniform application of radiation to the wall of the artery. The internal lumen 30 containing the radiation nodes 38 of the radiation source wire 36 is preferably located on a central axis of the catheter body. It is understood however that the internal lumen can be located on any axis in the body of the catheter, provided that the set of radiation nodes or other source of radiation, is located centrally within the artery when the balloon lobes of the inflation region , they inflate. The distal portion of the catheter assembly 10 is flexible wherein the inflatable balloon lobes 14, 16 and 18 are located, such that a tortuous artery can easily navigate as the catheter assembly is advanced over the guide wire 28. The wire Radiation source 36 will have to be centered within the artery, even when the area where the radiation is going to be delivered is the curved portion of the artery. Accordingly, as illustrated in Figure 3, the inflatable lobes are spaced so as to center the radiation source wire 36, even over the curved portion of the artery. The catheter body 11 is flexible and easily adapts to the curved portion of the artery. The inflation region 12 expands in contact with the artery and centers the radiation source wire 36 and the radiation nodes 38 within the artery. Radiation nodes 38 must deliver a radiation dose uniformly, in equal amounts to all portions of the affected artery. In a method for delivering a radioactive dose to a coronary artery in order to prevent restenosis, the catheter assembly is placed through the portion of the arterial passageway where a prior PTCA, arthrectomy procedure, laser ablation or similar procedures are performed. . The steps of the method as illustrated in the flow diagram of Figure 4 will be discussed in connection with Figures 5 to 10. In the introduction step 40, the catheter is introduced to the treatment site, such as the arterial site in where an angioplasty procedure has been performed. The catheter assembly 10 can be loaded from the back on the wire 28 as illustrated in Figure 5, which is already in place through the injury from the previous PTCA procedure. The catheter should be positioned so that the inflation region is located at the treatment site. The guidewire can alternatively be used in an over-the-wire assembly or for a rapid exchange type of catheter. In a quick exchange assembly, the proximal end of the guide wire is maintained manually while the rapid exchange catheter assembly is advanced over the guidewire to a desired location within the patient's artery, such as when a prior vascular procedure has been performed. A rapid exchange catheter is described in U.S. Pat. No. 5,458,613. The catheter assembly in a rapid exchange catheter includes a lateral wall port in the catheter body. The side wall port leads to the supply lumen or to a separate guide wire lumen. A small minimum profile for the catheter body can be maintained by causing the sidewall port to lead to the delivery lumen instead of forming a completely separate guidewire lumen. In the inflation stage 42, the inflation of the balloon lobes keeps the artery open at the treatment site and centers the supply lumen in the artery. The guidewire is then removed from the catheter assembly. As illustrated in Figure 6, the guide wire 28 is withdrawn through the proximal end of a mode of catheter assembly 10. The perfusion ports allow blood to circulate through the delivery lumen and beyond the inflation region. while the lobes of the balloon are inflated. In the loading stage 44, once the inflation region expands, the blind internal lumen is loaded to the delivery lumen of the catheter assembly on the support mandrel. As illustrated in Figure 7, the support mandrel 52 supports the blind internal lumen 30 during loading to the supply lumen 26. The support mandrel 52 is sufficiently rigid to prevent the blind internal lumen 30 from collapsing on itself during loading, and sufficiently flexible to allow external loading while the catheter is placed in the vasculature of the patient. The internal lumen 30 is loaded such that the blind distal end 32 is adjacent to the distal end of the inflation region 12. The proximal end of the internal lumen includes a Luer coupling 53, to provide access to the radiation source wire toward the assembly of catheter through the internal lumen. It should be understood that instead of a common Luer fitting 53, specialized custom fittings may be convenient to avoid accidental bad connections, ensuring that the various components connect only at the preferred sites. In the removal step 46, the support mandrel 52 is removed from the delivery lumen through the proximal end of the catheter assembly 10, as illustrated in Figure 8. The Luer accessory 53 remains coupled with the port at the proximal end of the catheter assembly 10. In the connection stage 48, the catheter is then connected to a radiation storage facility that automatically charges the radiation source wire into the blind internal lumen. As illustrated in Figure 9, the irradiation storage facility 54 is connected to the blind internal lumen of the catheter and the doctor activates the facility to advance and load a pre-determined portion of radiation source wire into the catheter assembly. The radiation source wire 36 from the storage facility 54 is inserted into the proximal end of the blind internal lumen through the Luer fitting 53. In the advancing step 50, as illustrated in Figure 10, the radiation source wire 36 it is loaded into the inner lumen 30 until the distal end of the wire containing the radioactive source material reaches the blind distant end 32 of the internal lumen 30. The source of radiation is placed in the portion of the coronary artery that is to receive the dose of radiation. The balloon lobes of the inflation region 12 are maintained in the expanded inflated condition for a sufficient amount of time to allow a therapeutically significant amount of radiation to treat the area and prevent restenosis. The inflation region when it expands, presses against the wall of the artery and centers the radiation source wire 36 and the source of radiation 38 with respect to the walls of the artery. Focusing the radiation dose allows all portions of the artery to receive even and equal amounts of radiation therapy. After the radiation dose has been administered to the treatment area to prevent restenosis, the radiation source wire 36 can be removed from the catheter assembly and directed back into the storage facility 54, and the inflation region 12 can be deflated and contract. The catheter assembly 10 can then be removed from the location within the vasculature of the patient. Other modifications to the present invention may be made without departing from its scope. Specific dimensions, doses, times and construction materials are given as examples and substitutes are readily contemplated which do not depart from the invention. It will be recognized by those skilled in the art that catheter assembly can be employed within a patient's vasculature system after different vascular procedures have been performed to a PRCA or atherectomy procedure. The scope of the invention shall not be limited except by the appended claims:

Claims (22)

1. CLAIMS 1. - An intravascular catheter for maintaining the opening of a body lumen during radiation supply to the body lumen, the catheter being characterized in that it comprises: a catheter body having a proximal end and a distal end; an inflation region disposed at the distal end of the catheter body, the inflation region has at least two lobes, the lobes contain the body lumen when inflated; and the catheter body further includes an internal lumen extending from the proximal end of the catheter body and adapted to receive a radiation source wire at the proximal end to advance to the inflation region, thereby inflating the lobes In the inflation region, the wire source of radiation is centered within the body lumen.
2. 2. - The catheter according to claim 1, characterized in that the internal lumen includes a closed distant end terminating at a point near the distal end of the inflation region, whereby the closed remote end of the internal lumen does not open to the body lumen, so that the radiation source wire is not exposed to body fluids.
3. 3. - The catheter according to claim 1, characterized in that the catheter body further includes a supply lumen adapted to receive a guidewire to place the catheter body in the body lumen, and wherein the supply lumen is adapted to receive the internal lumen after the guidewire is removed following the placement of the catheter body in the body lumen.
4. 4. The catheter according to claim 3, characterized in that the internal lumen includes a distal end terminating at a point near the distal end of the inflation region, wherein the distal end of the internal lumen does not open to the body lumen, thus avoiding contamination of the radiation source wire.
5. 5. - The catheter according to claim 1, characterized in that the catheter body further includes perfusion ports in fluid communication with the delivery lumen to allow blood perfusion while at least one of the lobes is inflated.
6. 6. - An intravascular catheter for maintaining the opening of a body lumen during radiation supply to the body lumen, the catheter being characterized in that it comprises: a catheter body having a proximal end and a distal end; an inflation region disposed at the distal end of the catheter body, the inflation region has at least two lobes, the lobes contact the body lumen when inflated; and a radiation source located within the inflation region, to arrange the radiation source in the body lumen such that substantially equal amounts of radiation energy are directed to the body lumen when the inflation region is inflated.
7. 7. - The catheter according to claim 6, characterized in that it further comprises a radiation source wire that includes a proximal end and a distal end having the associated radiation source.
8. 8. - The catheter according to claim 7 characterized in that the catheter body further includes an internal lumen extending from the proximal end of the catheter body and the internal lumen is adapted to receive the radiation source wire at the proximal end to advance to the inflation region, whereby the inflation of the lobe in the inflation region centers the radiation source wire inside the body lumen.
9. 9. - The catheter according to claim 8, characterized in that the catheter body further includes a delivery lumen adapted to receive a guidewire, to place the catheter body in the body lumen, and wherein the delivery lumen is It adapts to receive the internal lumen after the guidewire is removed following the placement of the catheter body in the body lumen.
10. 10. The catheter in accordance with the claim 9, characterized in that the catheter body further includes perfusion orifices in fluid communication with the blood flow and with perfusion channels thereby allowing blood perfusion while at least one of the lobes is inflated.
11. 11. - The catheter according to claim 9, characterized in that the internal lumen includes a distal end terminating at a point near the distal end of the inflation region, where the distal end of the internal lumen does not open to the body lumen, avoiding This way contamination of the wire source of radiation.
12. 12. The catheter according to claim 8, characterized in that the internal lumen includes a distal end terminating at a point near the distal end of the inflation region, wherein the distal end of the internal lumen does not open to the body lumen, thus avoiding contamination of the radiation source wire.
13. 13. - The catheter according to claim 12, characterized in that the radiation source delivers a low dose of radiation to the body lumen at a position adjacent to the distal end of the internal lumen.
14. 14. The catheter according to claim 6, characterized in that the inflation region is configured to center the source of radiation within the body lumen, such that substantially equal amounts of radiation energy are directed to the body lumen.
15. 15. The catheter according to claim 6, characterized in that the lobes of the inflation region center the source of radiation in the body lumen, when the lobes are inflated, each lobe has a substantially flat area when inflated.
16. 16. - An intravascular catheter for maintaining the opening of a body lumen during radiation delivery to the body lumen, the catheter being characterized in that it comprises: a catheter body having a proximal end and a distal end; an inflation region disposed at the distal end of the catheter body, the inflation region has at least two lobes, the lobes contact the body lumen when the lobes are inflated; a radiation source wire having a proximal end and a distal end; a source of radiation located at the far end of the radiation source wire; and an internal lumen extending from the proximal end of the catheter body, the inner lumen has a distal end terminating at a point near the distal end of the inflation region, the inner lumen is adapted to receive a radiation source wire at the proximal end for advancing to the inflation region, wherein the distal end of the internal lumen does not open to the body lumen, thus avoiding contamination of the radiation source wire; and inflation of the lobes in the inflation region centers the radiation source within the body lumen such that substantially equal amounts of radiation energy are directed to the body lumen.
17. 17. - The catheter according to claim 16, characterized in that the catheter body includes a delivery lumen adapted to receive a guidewire, the catheter body advances on the guide wire in the body lumen, and wherein the lumen of The delivery is configured to receive the internal lumen after the guidewire is removed following the placement of the catheter body in the body lumen.
18. 18. - The catheter according to claim 17, characterized in that the catheter body includes perfusion orifices in fluid communication with the blood flow and with perfusion channels that allow the blood to pass while at least one of the lobes is inflated .
19. 19. The catheter according to claim 16, characterized in that the radiation source delivers a low dose of radiation to the body lumen at a position adjacent to the distal end of the internal lumen.
20. 20. The catheter in accordance with the claim 16, characterized in that the inflation region is configured to center the source of radiation within the body lumen such that substantially equal amounts of radiation energy are directed to the body lumen.
21. 21. The catheter in accordance with the claim 16, characterized in that the lobes of the inflation region center the source of radiation in the body lumen when the lobes are inflated, each lobe having a substantially flat region that is formed on the lobe when inflated. _á-MtaU_-i_-.
22. 22. - Method for maintaining the opening of a body lumen and supplying radiation to the body lumen, the method is characterized in that it comprises the steps of: introducing a catheter having a proximal end and a distant end to a treatment site in the body lumen; dilate or expand an inflation region disposed at the distal end of the catheter; the inflation region has at least two lobes; charging a radiation source wire having a distal end and having a radiation source at its distal end, within an internal lumen in the catheter; advancing the distal end of the radiation source wire through the inner lumen to the inflation region, such that the radiation source is centered within the body lumen and substantially equal amounts of radiation energy are directed to the body lumen, while the inflation region expands; and maintaining the source of radiation in the inflation region for a sufficient time to deliver a therapeutically significant dose of radiation to the treatment site in the body lumen. _---- a _-- tü - ji_i --- i