Abstract:
The present invention provides an apparatus and method for the internal treatment of body cavities and damaged internal vessels using irradiation. A device and method according to the invention may be used to irradiate an internal tissue surface, for example, for the treatment of an aneurysm, tissue welding, or the removal of a stenosis in a blood vessel. In one embodiment, the invention provides a device for illuminating a body surface including a shaft having a light guide, a control unit, and a light scatterer. The control unit includes a light source optically coupled to the light guide; and the light scatterer is optically coupled to the light guide. The light scatterer includes a first, rear surface and a second, forward illuminating surface, and the light scatterer has a first undeployed, collapsed configuration and a second deployed configuration in which the illuminating surface has a larger caliber than in the first undeployed, collapsed configuration. In another embodiment, the invention provides an implantable device for irradiating a body surface comprising a shaft having a light source consisting of fiber optics or light emitting diodes embedded thereon. Activation and control of the energy emitted by the light source may be controlled by direct connection of wires, or remotely controlled by an external wireless remote control set.

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
       [0001]    This application claims priority from U.S. Application No. 61/110,659, filed Nov. 3, 2008, incorporated by reference in its entirety. 
     
    
     BACKGROUND 
       [0002]    This invention relates to medical devices and more specifically to such devices for internal irradiation of the body. 
         [0003]    Application of light to a tissue surface has been used in several medical treatments. For example, it is known to apply light to a tissue surface in order to heal a pathological state, to remove a stenosis in a blood vessel or for laser welding of tissues, for example in order to treat a rupture in a vessel wall or to perform an anastomosis of two blood vessels. It is believed that irradiating an aneurysmal blood vessel with low level laser irradiation retards progression of the aneurysm by bio-stimulating the vessel wall to produce extracellular matrix and reduce inflammation. It is also known to use application of light for tissue regeneration and therapy. For example, low level laser irradiation in the visible to far-red range of the light spectrum has been clinically shown to accelerate wound healing in skin wounds, and reduce pain and inflammation in musculoskeletal disorders. 
         [0004]    The underlying mechanisms are initiating processes such as collagen synthesis, cell proliferation, and reduction of expression and secretion of inflammatory markers. Gavish et al.,  Lasers in Surgery and Medicine  (2006) 38:779-786, which is incorporated herein by reference, discloses that low level laser in vitro stimulates vascular smooth muscle cell proliferation and collagen synthesis, modulates the equilibrium between regulatory matrix remodeling enzymes, and inhibits pro-inflammatory IL-1-β gene expression. In addition, Gavish et al.,  Lasers in Surgery and Medicine  (2008) 40(5): 371-378 which too is incorporated herein by reference, reports that low level laser irradiation of stimulated macrophages inhibits gene expression of monocyte chemotactic protein (MCP-1) as well as the pro-inflammatory cytokines, interleukin (IL)-1a, IL-1b, and IL-6 (and even the anti-inflammatory cytokine IL-10) and downregulates the secretion of pro-inflammatory proteins such as MCP-1 and IL1-beta. These properties of low level laser irradiation would appear to be of profound therapeutic relevance for arterial diseases such as aneurysm where inflammatory processes and weakening of the matrix structure of the arterial wall are the principal underlying pathologic components. 
         [0005]    An apparatus has been described for applying light to the heart tissue for a biostimulative and cytoprotective effect, which includes a source of electromagnetic radiation and optics operatively connected to the source of electromagnetic radiation. 
         [0006]    Additionally, low energy light exposure has been found to both inhibit restenosis following dilation of a stenotic region, and to inhibit vascular spasms, whether or not they are associated with a stenotic region. Such light energy has also been found to arrest progress of a stenosis and expose a vessel wall to light energy from an intravascular approach for the prevention of restenosis. An apparatus has been described for exposing the vessel wall to light using a light angioplasty catheter for the prevention of restenosis. 
         [0007]    It is also known that an apparatus may be used for applying light to the interior surface of a vascular wall for laser treatment of the vessel. Light may be generated by an extracorporeal light source guided by a light guide to the interior of the blood vessel to be treated. A light deflector and diffusor may be used to direct the light in a substantially radial fashion onto the vessel wall. 
         [0008]    Abdominal Aortic Aneurysm (AAA) formation is an arteriosclerotic process characterized by marked disruption of the musculo-elastic lamellar structure of the media. Extensive destruction of the wall matrix proteins including collagen and elastic tissue is associated with marked inflammatory cell infiltration and progressive diminution in the number of viable smooth muscle cells. Over time, and aggravated by contributory risk factors such as systolic hypertension, aneurysm growth occurs through a complicated, but insidious, imbalance between matrix protein production and degradation, favoring expansion, thereby increasing the risk of rupture of the weakened wall. 
         [0009]    AAA is present in approximately 10% of individuals over the age of 65 years, with its frequency increasing as the proportion of elderly individuals in the general population continues to rise. It is widely known that the risk of rupture increases in approximate proportion to aneurysm size, which can be monitored by computed tomography (CT), ultrasound, or magnetic resonance imaging (MRI). The estimated risk of rupture ranges from 10-20% for an abdominal aneurysm 6-7 cm in diameter, to 30-50% if the maximum diameter is greater than 8 cm. Overall mortality from a ruptured AAA is greater than 90%. 
         [0010]    Current forms of aneurysm treatment focus either on the open abdomen, surgical, graft-based repair or endovascular exclusion of the diseased segment of aorta with large, membrane-covered, e.g. Gortex covered stents. Both techniques have major side effects with potentially life-threatening consequences, particularly in patients of advanced age (the majority of patients) or others at high risk or compromised cardiac function. 
         [0011]    Increased detection of AAA at early stages of the disease and the severe complications often associated with currently available surgical and endovascular repair have emphasized the need for alternative therapeutic strategies that target pathogenetic mechanisms of progression and rupture. 
         [0012]    While the techniques described in the above references describe generally the benefits of the techniques and methods for using the electromagnetic spectrum to treat tissue surfaces, the use of a remote light source and optical paths can create difficulties in the in vitro use of the processes and apparatus in the prior art, such as localized heating, and are not intended to be placed for long periods of time to vary the form and energy of treatment of the tissue. Accordingly, the present invention provides an apparatus for the treatment of an interior surface of a damaged vessel or internal body cavity by light energy. 
       SUMMARY OF THE INVENTION 
       [0013]    The present invention provides an apparatus and method for the internal treatment of surfaces of body cavities and damaged internal vessels using irradiation. A device and method according to the invention may be used to radiate an internal tissue surface, for example, for the treatment of an aneurysm, tissue welding, or the removal of a stenosis in a blood vessel. 
         [0014]    In its first aspect, the present invention provides a device for illuminating a tissue surface. The illuminating device of the invention has a slender shaft that may be rigid or flexible, as required in any application. Light is irradiated from the distal end of the shaft. In one preferred embodiment, the shaft is connected at its proximal end to a light source, that may be, for example, a laser. Light generated by a light source at the proximal end of the shaft is conducted through the shaft via a light guide to the distal end of the shaft. Alternatively, a light source, such as a light emitting diode(s) (LED) may be positioned at the distal end of the shaft. A light scatterer is positioned at the distal end of the shaft that is optically coupled to the light guide. Light emerging from the distal end of the light guide is scattered by the light scatterer so that light emerges from the light scatter from an illuminating surface having an area that is larger than the cross-sectional area of the light guide The illuminating surface is transformable between an undeployed, small caliber configuration in which it is delivered to the tissue surface to be treated, and a deployed, large caliber configuration in which the treatment is delivered. In the deployed configuration, the illuminating surface is preferably shaped to conform to the surface to be radiated so that the illuminating surface can be applied onto the surface to be radiated. For example, for illuminating the perivascular (adventitial) surface of a blood vessel, the deployed illuminating surface would preferably have a partial cylindrical surface. As explained below, this enhances coupling and homogeneity of the light radiated from the illuminating surface and radiation of the surface to be treated. At the conclusion of the treatment, the illuminating surface is brought to its small caliber undeployed configuration, and the device is removed from the body. 
         [0015]    This device is designed for illuminating/irradiating an internal body organ such as, but not limited to an aneurysmatic artery or vein, e.g., an abdominal aortic aneurysm, carotid artery aneurysm, popliteal artery aneurysm, cerebral artery aneurysm, or coronary artery aneurysm. Irradiation of such arterial walls or other organs can be through its perivascular (or periorganal) or endoluminal (or intracavity) surface of an artery or organ. 
         [0016]    The device can be powered by an energy source that is located in a variety of positions including, but not limited to: within a body cavity, in a subcutaneous position (e.g. lateral pectoral area similar, but not limited to, the site of positioning of cardiac pacemaker batteries), or in an external position either carried as a purse or any method of transport or positioning. 
         [0017]    The device can be connected to its energy source either by immediate juxtaposition or by means of connecting wires which may, in one configuration, pierce the body wall to enter the energy source located in, but not limited to, the subcutaneous position. 
         [0018]    Power and duration of the emitted radiation from the device as well as other physical, optical, electrical, and other parameters can be controlled in wireless fashion from outside the body cavity by a portable remote control set. 
         [0019]    In one preferred embodiment, the light scatterer of the device is adapted to be implanted inside the body with the illuminating surface in its deployed configuration and affixed to the body surface to be illuminated. This allows repeated illumination sessions without removing the light scatterer from the body. In one embodiment of the utilizing an implantable light scatterer, the control unit communicates with the light scattered via the shaft which extends from the light scatterer to the control unit passing through an incision in the skin. The controller may be portable, in which case it could remain attached to the proximal end of the shaft as the user moves around, so that illumination of the body surface could be carried out at any time as required. Alternatively, the control unit may be detachable from the shaft. In this case, the controller would be attached to the shaft at the times when the body surface is to be illuminated. When an implantable light scatterer is used, the light source may be located in the control unit, in which case light from the light source is conducted to the light scatterer by the light guide. In one embodiment, the light source is implanted together with the illuminating surface. The light source could be connected to the control unit by electrical wires. Alternatively, an energy source for the light source, such as a rechargeable battery, could be implanted together with the light source. In this case, the light source could be provided with a remote control switch for switching of the light on and off that is controlled via wireless communication with the control unit. 
         [0020]    The illuminating device of the invention may be provided with means for firmly attaching the deployed illuminating surface to the tissue surface to be treated. Such means may comprise, for example, use of suction or attachment hooks. 
         [0021]    The light source is selected in accordance with the requirements of the particular application. For example, in order to treat an aneurysm, low level laser irradiation (also known as “low energy laser”, “photo-biostimulation” and “red-light therapy”) in the range of 500 to 900 nm, and more preferably in the range of 600 to 900 nm, may be used that is preferably emitted from the illuminating surface with an energy flux in the range of about 0.01 to about 50 Joules/cm 2 , and more preferably from about 0.1 to about 5 Joules/cm 2 . For surgical welding, light in the 780 to 2010 nm range may be used, in which case the light source may be a semiconductor diode laser that generates 808 nm light or a diode-pumped Ho:Y AG laser which generates 2010 nm light. 
         [0022]    In its second aspect, the invention provides a method for treating a tissue surface. In accordance with this aspect of the invention, the distal end of the illuminating device of the invention is delivered, with the light illuminating surface in its undeployed configuration to the body site to be treated. The light illuminating surface is then brought to its deployed configuration and is applied to the surface to be treated, and the surface to be treated is radiated. At the conclusion of the radiation, the light illuminating surface is removed from the body surface and the light illuminating surface is brought into its undeployed configuration and the device is removed from the body. 
         [0023]    The device and method of the invention may be used for illuminating the perivascular surface of a blood vessel, for example, in order to treat an aneurysm. Without wishing to be bound by a particular theory, it is believed that irradiating an aneurysmal blood vessel with low level laser irradiation retards progression of the aneurysm by bio-stimulating the vessel wall to increase smooth muscle cell proliferation, increase extracellular matrix protein production and reduce inflammation. 
         [0024]    In one embodiment, the invention provides a device for illuminating a body surface including a shaft having a light guide, a control unit, and a light scatterer. The control unit includes a light source optically coupled to the light guide; and the light scatterer is optically coupled to the light guide. The light scatterer includes a first, rear surface and a second, forward illuminating surface, and the light scatterer has a first undeployed, collapsed configuration and a second deployed configuration in which the illuminating surface has a larger caliber than in the first undeployed, collapsed configuration. 
         [0025]    In an alternative embodiment, the invention provides a device for illuminating a body surface which includes an elongated shaft having a light guide, a light source optically coupled to the end of the light guide and illuminating light having a wavelength in the range of 500 to 900 nm, and a light scatterer optically coupled to the end of the light guide. 
         [0026]    In another embodiment, the invention also provides a method for illuminating a body surface, which includes providing a device for illuminating a body surface, the device including: a shaft including a light guide, a control unit including a light source optically coupled to the light guide; and a light scatterer optically coupled to the light guide, the light scatterer including a first, rear surface and a second, forward illuminating surface, and the light scatterer having a first undeployed, collapsed configuration and a second deployed configuration in which the illuminating surface has a larger caliber than in said first undeployed, collapsed configuration; delivering the distal end of the shaft to the body surface with the light scatterer in the first undeployed, collapsed configuration; causing the light scatterer to move from the first undeployed, collapsed configuration to the second deployed configuration; applying the illuminating surface to the body surface; and illuminating the body surface from the light source. 
         [0027]    In an alternative embodiment, the invention provides a method for treating an aneurysmal blood vessel including irradiating the blood vessel with radiation having a wavelength from 500 to 900 nm. 
         [0028]    In another embodiment, the invention provides an implantable device for irradiating a body surface comprising a shaft having a light source consisting of fiber optics or light emitting diodes embedded thereon. Activation and control of the energy emitted by the light source may be controlled by direct connection of wires, or remotely controlled by an external wireless remote control set. The programmability of the external power source allows for the control and variation of the radiation therapy used, and the radiation frequency at which it is applied without the requirement to move or alter the coverage of the light source. 
         [0029]    Other features and advantages of the present invention will become more apparent from the following detailed description of the preferred embodiments in conjunction with the accompanying drawings, which illustrate, by way of example, the operation of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0030]    In order to understand the invention and to see how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which: 
           [0031]      FIGS. 1   a  and  1   b  show a device for illuminating a tissue surface in accordance with one embodiment of the invention; 
           [0032]      FIGS. 2   a  and  2   b  show a device for illuminating a tissue surface in accordance with a second embodiment of the invention; 
           [0033]      FIGS. 3   a  and  3   b  show a device for illuminating a tissue surface in accordance with a third embodiment of the invention; and 
           [0034]      FIGS. 4   a  to  4   d  show use of the device of the invention for treating an aneurysm. 
           [0035]      FIG. 5  shows morphometric ultrasonographic measurements of the supra-renal aneurysm prone segment of the subject and the adjacent inter-renal non-aneurysm prone segments of the subject. 
           [0036]      FIG. 6  shows a suprarenal abdominal aortic aneurysm 4 weeks after angiotensin II infusion in the apolipoprotein e-deficient mouse (right) not present in similar mouse treated with low level laser irradiation (left). 
           [0037]      FIG. 7  shows high-frequency two-dimensional (B-mode) ultrasound measurements of the aortas of control and low level laser irradiated angiotensin II (Ang II) infused apolipoprotein e-deficient mice at baseline and after 4 weeks. 
           [0038]      FIG. 8  shows the effect of LLLI on aneurysmal dilatiation of the suprarenal aneurysm-prone aortic segment of angiotensin II-infused apolipoprotein e-deficient mice. 
           [0039]      FIG. 9  shows M-mode images of suprarenal aneurysm-prone segments showing marked decrease in radial wall velocity (slope)(RWV) in the severely dilated aorta of the untreated mouse 4 weeks after angiotensin infusion (right) compared to baseline (upper left). 
           [0040]      FIG. 10  shows the effect of LLLI on radial wall velocity of the suprarenal Aneurysm Prone Aortic Segment. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0041]    The present invention shows a device in  FIG. 1 , generally indicated by  10 , for illuminating a tissue surface to be treated, in accordance with one embodiment of the invention. The tissue surface may be, for example, the outer surface of a blood vessel where an aneurysm has formed. The illuminating device has a slender shaft  11 , shown in longitudinal section in  FIG. 1 , having a proximal end  15  and a distal end  17 . The shaft  11  may be rigid or flexible, as required in any application. The shaft  11  has a sheath  13  surrounding a light guide  20  that may consist of a single optical fiber or a bundle of optical fibers. The al fiber is typically made from glass. 
         [0042]    The shaft  11  is connected at its proximal end  15  to a control unit  14  that houses a light source  9 , that may be, for example, a laser. Light generated by the light source  9 , enters the light guide  20  and is conducted through the light guide  20  to the distal end of the light guide  20 . Since the end face  26  of the distal end of the light guide  20  is flat, the pencil of light emerging from the end face  26  will have a cross-sectional area essentially equal to the cross-sectional area of the light guide  20 . Thus, in accordance with the invention, in order to increase the radiated area, the radiation device  10  further comprises a light scatterer  23  positioned at the distal end of the light guide  20 , that is optically coupled to the light guide  20 . The light scatterer  23  has a deployed configuration shown in  FIG. 1   a  in which an illuminating surface  29  has a large caliber configuration. Light emitted from the end face  26  of the light guide  20  enters the light scatterer  23  at a first surface  25  and is scattered through the light scatterer  23 . The light is then emitted from the illuminating surface  29 , as indicated by the arrows  27  to radiate the site to be treated, as described below. The illuminating surface has an area that is greater than the cross-sectional area of the light guide  20 . In the deployed configuration, the illuminating surface  29  is preferably shaped to conform to the surface to be radiated so that the illuminating surface can be applied onto the surface to be radiated. For example, for illuminating the outer surface of a blood vessel, the illuminating surface  29  would be a partial cylindrical surface, as shown in  FIG. 1   a . As explained below, this enhances coupling of the light radiated from the illuminating surface and radiation of the surface to be treated. The light scatterer is preferably provided with a light reflecting coating  32  on its rear surface in order to reflect back scattered light in the light scatterer in the direction of the arrows  27 . 
         [0043]    The light scatterer  23  also has an undeployed configuration shown in  FIG. 1   b  in which the illuminating surface  29  is collapsed into a small caliber configuration. In the embodiment shown in  FIG. 1 , the light scatterer  23  is formed from a resiliently flexible material. The light scatterer may be made, for example, from transparent silicon rubber in which a light scattering substance is embedded. Alternatively, the light scatterer may include one or more lenses (not shown). In this embodiment, the shaft  11  includes a constraining sleeve  30  that surrounds the sheath  13 . In the undeployed configuration shown in  FIG. 1   b , the light scatterer  23  is constricted into its small caliber undeployed configuration and is maintained in the undeployed configuration by means of the constraining sleeve  30 . The constraining sleeve  30  is slidable axially along the shaft  11  from a forward position shown in  FIG. 1   b  and a rearward position shown in  FIG. 1   a . In the forward position ( FIG. 1   b ), the sleeve  30  extends beyond the end of the optic fiber  20  with the light scatterer  23  collapsed in the interior of the sleeve  30 . When the sleeve  30  is brought to its rearward position ( FIG. 1   a ) the sleeve  30  is retracted from the light scatterer  30  and the light scatterer  23  spontaneously assumes its deployed, large caliber configuration due to the resiliently flexible character of the light scatterer  23 . In order to slide the sleeve  30  between its forward and rearward position, a user may grasp the sleeve  30  at its proximal end and manually slide the sleeve over the sheath  13 . 
         [0044]    The illuminating device  10  may further be configured for connection to a source of negative pressure. As shown in  FIG. 1 , for this purpose, the shaft may include a channel  12  extending from a valve  3  adapted for connection to a source of negative pressure (not shown) at the proximal end of the shaft  11  through the shaft  11  to the distal end of the shaft. As explained below, generation of negative pressure at the distal end of the light scatterer  23  is used to attach the light scatterer  23  to the tissue surface and to immobilize the light scatterer on the tissue surface during radiation. 
         [0045]    The shaft  11  may optionally contain a working channel (not shown) in order to accommodate a guide wire or working tool, as required in any application. 
         [0046]    The control unit  14  is provided with a user input device, such as a keypad  34  to allow the user to select one or more parameters of the treatment, such as the radiation intensity or fluency. The control unit may also have a display  36  such as a screen  38  displaying the selected parameters and other relevant information. 
         [0047]    In one preferred embodiment, the light scatterer  23  of the device is adapted to be implanted inside the body with the illuminating surface  29  in its deployed configuration and affixed to the body surface to be illuminated. This allows repeated illumination sessions without removing the light scatterer from the body. In one embodiment of the utilizing implantable light scatter, the control unit  14  communicates with the light scatterer  23  via the shaft  11  which extends from the light scatterer  23  to the control unit  14 , passing through an incision in the skin. The controller may be portable, in which case it could remain attached to the proximal end of the shaft as the user moves around, so that illumination of the body surface could be carried out at any time as required. Alternatively, the control unit may be detachable from the shaft. In this case, the controller would be attached to the shaft at the times when the body surface is to be illuminated. When an implantable light scatterer is used, the light source may be located in the control unit, in which case light from the light source is conducted to the light scatterer by the light guide  20 . In one embodiment, the light source is implanted together with the illuminating surface. The light source could be connected to the control unit by electrical wires. Alternatively, an energy source for the light source, such as a rechargeable battery, could be implanted together with the light source. In this case, the light source could be provided with a remote control switch for switching of the light on and off that is controlled via wireless communication with the control unit. 
         [0048]      FIGS. 2   a  and  2   b  show a device, generally indicated by  40 , for illuminating a tissue surface to be treated, in accordance with another embodiment of the invention. The tissue illuminating device  40  has several components in common with the device  10  described above in reference to  FIG. 1 , and similar components are indicated by the same reference numerals in  FIGS. 1   a  and  1   b  and  2   a  and  2   b  without further comment. The illuminating device has a slender shaft  41 , shown in longitudinal section in  FIG. 2 , having a proximal end  45  and a distal end  47 . The shaft  41  may be rigid or flexible, as required in any application. The shaft  41  has a sheath  43  surrounding a light guide  20  that may consist of a single optical fiber or a bundle of optical fibers. 
         [0049]    The device  40  includes a light scatterer  48  at the distal end  47  of the shaft that is optically coupled to the light guide  20 . The light scatterer  48  has a large caliber deployed configuration shown in  FIG. 2   a , and a small caliber undeployed configuration shown in  FIG. 2   b . In this embodiment, the light scatterer  48  includes a pleated sheet containing two or more panels  50  that are hinged together by hinges  52 . In the undeployed configuration ( FIG. 2   b ) the pleated sheet is folded into the small caliber, while in the deployed configuration ( FIG. 2   a ) the pleated sheet is extended. The panels may be formed from transparent silicone rubber in which a light scattering substance is embedded. Light emitted from the end face  26  of the light guide  20  enters the light scatterer  48  at a first surface  45  and is scattered through the light scatterer  48 . The light is then emitted from an illuminating surface  49  on each panel in an essentially forward direction, as indicated by the arrows  53  to radiate the site to be treated. In the deployed configuration, the illuminating surface  49  is preferably shaped to conform to the surface to be radiated so that the illuminating surface can be applied onto the surface to be radiated. The light scatterer is preferably provided with a light reflecting coating  59  on its rear surface in order to reflect back scattered light in the light scatterer in the direction of the arrows  53 . The reflecting coating  59  may be made, from a biocompatible shiny material, deposited on the rear surface of the light scatterer. 
         [0050]    The light scatterer  48  further includes an actuating mechanism for transforming the light scatterer  48  between its deployed and undeployed configurations. The hinges  52  comprise one or more elements formed from a shape memory material such as Nitinol that has been trained to behave as described below. The hinges have a deployed configuration shown in  FIG. 2   a , and an undeployed configuration shown in  FIG. 2   b . The hinges are attached to the panels so that passage of the elements from their undeployed to their deployed configurations drives the passage of the light scatterer  48  between its undeployed configuration and its deployed configuration, and vice versa. 
         [0051]    The shaft  41  has a channel  60  for delivering a pressurized liquid such as physiological saline from a fluid source  62  located adjacent to, or inside, the control unit  14 . The fluid source  62  includes a temperature controlling system that allows the temperature of the fluid to be selected by a user. The fluid source  62  is in fluid contact with the channel  60  via a connecting hose  64 . When the light scatterer  48  in its undeployed configuration is to be brought to its deployed configuration, a pressurized fluid is used at a first temperature. The fluid is delivered to the distal end  47  of the shaft where it brings the temperature of the hinge elements to a temperature at which the shape memory material undergoes a first shape transition bringing the hinges  52  into their deployed configuration. When the light scatterer  48  in its deployed configuration is to be brought to its undeployed configuration, a pressurized fluid is used at a second temperature that is delivered to the distal end of the shaft where it brings the temperature of the hinges  52  to a temperature at which the shape memory material undergoes a second shape transition bringing the hinges  52  into their undeployed configuration. 
         [0052]      FIGS. 3   a  and  3   b  shows a device, generally indicated by  70 , for illuminating a tissue surface to be treated, in accordance with yet another embodiment of the invention. The tissue illuminating device  70  has several components in common with the device  10  described above in reference to  FIGS. 1   a  and  1   b , and similar components are indicated by the same reference numerals in  FIGS. 1   a ,  1   b ,  3   a , and  3   b , without further comment. The illuminating device has a slender shaft  71 , shown in longitudinal section in  FIG. 3 , having a proximal end  75  and a distal end  77 . The shaft  71  may be rigid or flexible, as required in any application. The shaft  71  has a sheath  73  surrounding a light guide  20  that may consist of a single optical fiber or a bundle of optical fibers. 
         [0053]    The device  70  includes a light scatterer  78  at the distal  77  of the shaft that is optically coupled to the light guide  20 . In this embodiment, the light scatterer  78  is an inflatable balloon that may be formed, for example, from transparent silicone rubber in which a light scattering substance is embedded. The light scatterer  78  has a large caliber deployed configuration shown in  FIGS. 3   a  and  3   b  in which the balloon is inflated, and a small caliber undeployed configuration shown in  FIG. 3   b  in which the balloon is deflated. In the deployed configuration, light emitted from the end face  26  of the light guide  20  enters the light scatterer  78  at a first surface  75  and is scattered through the light scatterer  78 . The light is then emitted from an illuminating surface  79  of the light scatterer  78  in an essentially forward direction, as indicated by the arrows  83  to radiate the site to be treated. In the deployed configuration, the illuminating surface  79  is preferably shaped to conform to the surface to be radiated so that the illuminating surface can be applied onto the surface to be radiated. The light scatterer is preferable provided with a light reflecting coating  89  on its rear surface in order to reflect back scattered light in the light scatterer in the direction of the arrows  83 . 
         [0054]    The shaft  71  has a channel  80  for delivering a pressurized fluid such as water or air from a fluid source  82  located adjacent to, or inside, the control unit  14 . The fluid source  82  is in fluid contact with the channel  80  via a connecting hose  84 . When the light scatterer  78  in its undeployed configuration is to be brought to its deployed configuration, the pressurized fluid is delivered to the distal end  47  of the shaft and inflates the balloon. When the light scatterer  78  in its deployed configuration is to be brought to its undeployed configuration, the fluid is pumped from the balloon back to the fluid source  82 . 
         [0055]      FIGS. 4   a  and  4   b  depict use of the device  40  in a surgical procedure in which an internal body surface is to be radiated. In the example, the surgical procedure is treatment of an aneurysm in the abdominal aorta  102 . This is by way of example only, and the device of the invention may be used to radiate any body surface. As shown in  FIGS. 4   a  and  4   b , the shaft  41  of the device  40 , with the light scatterer  48  in its undeployed configuration, is introduced through an incision at a first location  96  on the body surface of a subject  95  into a body cavity, which in this example, is an abdomen  99 . The surgical procedure may utilize laparoscopy, in which case an endoscope  97  is introduced into the abdomen  99  through a second incision at a second location  98  on the body surface. Abdominal body organs (not shown in  FIGS. 4   a - 4   d ) are moved aside in order to allow access to the aorta  102 . The endoscope  97  illuminates the abdomen  99  including the outer surface of the aorta  102 . The endoscope  97  is part of a laparoscopic imaging system that displays on a display screen (not shown), an image of the abdomen  99 , so as to allow a user  110  to observe the cavity  99  during the procedure. The abdomen  99  may temporarily be expanded in order to facilitate the maneuverability of the device  40  and the endoscope  97  in the abdomen  99 . 
         [0056]    In  FIG. 4   a , the device  40  has been maneuvered so as to bring the distal end  47  of the shaft  41  and the light scatterer  48  into proximity with the aorta  102 . At this point, the fluid in the fluid source  62  ( FIG. 2 ) is brought to the first temperature, and the fluid source  62  is then activated in order to deliver the fluid at the first temperature through the connecting hose  64  ( FIGS. 2   a  and  2   b ) and the channel  60  ( FIGS. 2   a  and  2   b ) to the distal end  47  of the shaft where it brings the hinge elements to a temperature in which they assume their deployed configuration. This brings the light scatterer  48  to its deployed configuration, as shown in  FIG. 4   b . The illuminating surface  49  of the light scatterer  48  in the deployed configuration of the light scatterer  48  has the shape of a partial cylindrical surface with a radius approximately equal to the outer radius of the aorta  102  to be radiated. The device  40  is then maneuvered in the abdomen  99  so as to apply the illuminating surface  49  to the outer surface of the aorta  102 , as shown in  FIG. 4   c . The valve  3  is then opened to deliver negative pressure to the light scatterer  48  so as to firmly apply the illuminating surface  49  to the aorta and to immobilize the light scatterer  48  on the outer surface of the aorta. The light source in the control unit  14  is then activated. Light from the light source is conducted along the light guide  20  to the light scatterer  48 . Essentially the entire surface area of the aorta that is in contact with the illuminating surface  49  is simultaneously radiated. 
         [0057]    When the radiation is completed, the negative pressure is discontinued to release the light scatterer  48  from the aorta. The fluid in the fluid source  62  is brought to the second temperature, and the fluid source  62  is then activated in order to deliver the fluid at the second temperature through the connecting hose  64  and the channel  60  to the distal end  47  of the shaft where it brings the hinge elements to a temperature in which they assume their undeployed configuration. This brings the light scatterer  48  back to its undeployed configuration, as shown in  FIG. 4   d . The device  40  is then removed from the abdomen  99 . 
         [0058]    Biological Experimental Data 
         [0059]    Study Design 
         [0060]    The effect of low level laser irradiation (LLLI) on AAA formation in the angiotensin II-infused apolipoprotein E-deficient (−/−) C57/Black mouse model was studied. This model was developed in the laboratory of Daugherty and colleagues. In this mouse model, suprarenal abdominal aortic aneurysms form in up to 80-85% of the cases. High frequency ultrasonography (HF-U/S) (0.01 mm resolution) was used in the laboratory in order to quantify the effect of LLLI on aortic expansion over time. This recently developed technology was designed specifically for non-invasive micro-imaging in mice. 
         [0061]    Angiotensin II was infused in twenty-eight male mice aged 12-13 weeks via subcutaneously implanted osmotic minipumps (see details below). Laparotomy was performed to enable direct irradiation of the aorta. Nine animals died during surgery, and 1 was disqualified as a result of pump extrusion. Of the 28 mice, 13 were irradiated and 15 were sham-operated, non-irradiated controls. 
         [0062]    Referring to  FIG. 5 , morphometric ultrasonographic measurements generally indicated by  110 , of the supra-renal aneurysm prone segment  112  and the adjacent inter-renal non-aneurysm prone segments  114  were performed at baseline and at 4 weeks after the onset of angiotensin II infusion. 
         [0063]    Mice 
         [0064]    The mice were bred in-house from stock originating from Jackson Laboratories. The mice were housed in a specific pathogen-free (SPF) environment. Water and normal diet were available ad libitum. The investigation conforms with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996). Animal care and the experimental procedures were approved by the Ethics Committee of the Faculty of Medicine of The Hebrew University, Jerusalem, Israel (MD-07-10349-3). 
         [0065]    Angiotensin II Infusion 
         [0066]    Osmotic minipumps (Alzet, model 2004, Durect Corp; Cupertino, Calif.) were filled with Angiotensin II (Calbiochem; La Jolla, Calif.) (infusion rate 1000 ng/kg/min). The pumps were implanted subcutaneously on the right flank through an incision in the scapular region and maintained for the entire 28 days—from the time of irradiation until sacrifice. 
         [0067]    Low Level Laser Irradiation (LLLI) 
         [0068]    A diode laser system coupled to an optic fiber was used with 0-450 mW power and 780 nm wavelength (BWTek, Newark, Del.). The irradiation box contained 2 compartments with a hole between. The laser was placed in the upper compartment with the optic fiber tip threaded through the hole above the irradiation plane at a distance adjusted for optimal expansion of the ray. The power was measured at the plane of the aorta with a Laser Mate power meter (Coherent, Auburn group, Europe). The exposed aorta was irradiated at 4 mW/cm for 9 minutes which accumulated to a total energy density of 2 J/cm. 
         [0069]    Surgical Protocol 
         [0070]    Mice were anesthetized by subcutaneous injection of ketamine (200 mg/kg) and xylazine (10 mg/kg). All animals received subcutaneous injections of cefamizine (30 mg/kg), Tramadol analgesia (2 mg/kg), and warmed saline (2 ml). Chloramphenicol ointment was applied locally to the conjunctival sacs to prevent corneal damage. The abdominal aorta was exposed through a left subcostal incision (retroperitoneal approach), and the region between the diaphragm and the renal arteries was isolated from the surrounding retroperitoneal structures. The mice were then placed in the irradiation box with the exposed abdominal aorta localized in the center of the beam. The sham-operated, non-irradiated control animals followed the same protocol but with the laser turned off. The Alzet minipump was implanted as described above. 
         [0071]    Ultrasound Imaging and Analysis 
         [0072]    The high resolution ultrasound imaging system Vevo 770, VisualSonics, Toronto, Canada) was used to perform two-dimensional (B-mode) and motion-mode (M-mode) imaging using a mechanical transducer (RMV707B) synchronized to the electrocardiographic signal. The transducer had a central frequency of 40 MHz, a focal length of 6 mm, a frame rate of 30 Hz, and an 8×8 mm field of view with spatial resolution of 30 μm. Scans were performed under anesthesia using 2% isofluorane. A longitudinal image of the abdominal aorta between the diaphragm and the renal arteries was acquired. Doppler signals were used to confirm the identification of the abdominal aorta. Transverse images at the level of the maximal dilatation of the aneurysm-prone suprarenal portion of the abdominal aorta were acquired in B-mode and M-mode with the adjacent, non-aneurysm-prone portion of the aorta between the right and left renal arteries serving as internal controls ( FIG. 1 ). The measurements were performed with VisualSonics proprietary software using multiple frames. The maximum aortic cross-sectional diameter (associated with systole) was determined from B-mode data. Diastolic diameter, systolic diameter, and maximal aortic radial wall velocity (RWV) (the first derivative [slope] of the aortic diameter with respect to time [dD/dt]) were determined from M-mode to assess the consistency and viscoelastic behavior of the arterial wall. Pulse diameter was calculated by subtracting diastolic from systolic aortic diameter and then normalizing to maximum systolic diameter to account for vessel size. 
         [0073]    For morphometric analysis, the number of individual mice with ≧50%, ≧40%, or ≧30% cross-sectional diameter expansion of the suprarenal aortic segments 28 days after baseline was determined for control and LLLI mice. In addition to the individual (categorical) data, the morphometric data were also analyzed after calculating the mean cross-sectional diameter across all animals in each group (continuous data). In order to account for any normal variations in vessel sizes between animals, measurements of the suprarenal segments were also normalized to the adjacent, non-dilated, internal control segments of each animal at the level between the origins of the left and right renal arteries. 
         [0074]    Categorical and continuous analyses were also conducted for the physiological parameters derived from M-mode data—pulse diameter normalized to systole and maximal radial wall velocity. The number of individual mice showing ≧75% reduction of pulse diameter and the number of mice showing ≧50% reduction in maximal RWV at endpoint over baseline were determined for control and LLLI mice. The means of these two parameters were calculated across all animals in each of the 4 groups. 
         [0075]    Statistical Analysis 
         [0076]    Categorical data were analyzed using Fisher&#39;s Exact Test with p&lt;0.05 considered significant. For continuous data, comparisons between measurements at baseline and at the 28-day endpoint in the same mice were performed by paired, 2-tailed t-test with the Bonferroni correction for multiple comparisons. Comparisons between control and LLLI mice at baseline or at the 28-day endpoint were performed by unpaired, 2 tailed t-test with the Bonferroni correction. 
         [0077]    Data from the M-mode measurements of one animal were excluded because of technical problems with the 28-day endpoint measurement. Data of radial wall velocity from one additional animal were excluded on basis of outlier analysis. 
         [0078]    Results 
         [0079]    Ultrasound measurements for each animal are presented in Table 1, shown below: 
         [0000]    
       
         
               
             
               
               
             
               
               
               
             
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Ultrasound Measurements 
               
             
          
           
               
                   
                 Time point 
               
             
          
           
               
                   
                 Baseline 
                 End point 
               
             
          
           
               
                   
                 Ultrasound mode 
               
             
          
           
               
                   
                 B-mode 
                 M-mode 
                 B-mode 
                 M-mode 
               
             
          
           
               
                 GROUP 
                 # 
                 MSR-B 
                 Ren-B 
                 Dias-B 
                 Syst-B 
                 Veloc-B 
                 MSR-E 
                 Ren-E 
                 Dias-E 
                 Syst-E 
                 Veloc-E 
               
               
                   
               
             
          
           
               
                 Control 
                 1 
                 1.14 
                 1.05 
                 1.02 
                 1.21 
                 4.3 
                 1.41 
                 0.94 
                 1.27 
                 1.37 
                 1.6 
               
               
                 Control 
                 2 
                 1.18 
                 0.94 
                 1.19 
                 1.31 
                 4.13 
                 1.51 
                 0.84 
                 1.41 
                 1.61 
                 3.31 
               
               
                 Control 
                 3 
                 1.16 
                 0.92 
                 1.19 
                 1.3 
                 3.23 
                 2.32 
                 0.84 
                 2.1 
                 2.11 
                 0.73 
               
               
                 Control 
                 4 
                 1.16 
                 0.99 
                 1.15 
                 1.3 
                 3.91 
                 1.7 
                 0.94 
                 1.73 
                 1.79 
                 1.6 
               
               
                 Control 
                 5 
                 1.05 
                 0.72 
                 1.04 
                 1.15 
                 2.46 
                 1.72 
                 0.96 
                 1.6 
                 1.7 
                 2.23 
               
               
                 Control 
                 6 
                 1.14 
                 0.86 
                 1.17 
                 1.32 
                 2.72 
                 1.69 
                 0.82 
                 1.54 
                 1.65 
                 2.95 
               
               
                 Control 
                 7 
                 1.06 
                 0.77 
                 1.02 
                 1.15 
                 3.02 
                 1.84 
                 0.94 
                 1.94 
                 2.1 
                 3.57 
               
               
                 Control 
                 8 
                 1.11 
                 0.88 
                 1.05 
                 1.2 
                 3.77 
                 1.96 
                 0.91 
                 1.33 
                 1.35 
                 1.37 
               
               
                 Control 
                 9 
                 1.11 
                 0.81 
                 1.16 
                 1.31 
                 3.92 
                 1.34 
                 0.96 
                 1.18 
                 1.42 
                 7.6* 
               
               
                 Control 
                 10 
                 1.17 
                 0.79 
                 1.05 
                 1.19 
                 3.64 
                 1.81 
                 1.05 
                 TP 
                 TP 
                 TP 
               
               
                 Control 
                 11 
                 1.08 
                 0.76 
                 0.96 
                 1.11 
                 4.67 
                 2.36 
                 1 
                 2.29 
                 2.34 
                 0.96 
               
               
                 Control 
                 12 
                 1 
                 0.83 
                 1.02 
                 1.17 
                 4.92 
                 1.58 
                 1.05 
                 1.29 
                 1.5 
                 4.52 
               
               
                 Control 
                 13 
                 1.22 
                 0.88 
                 1.09 
                 1.27 
                 3.5 
                 1.43 
                 1.05 
                 1.16 
                 1.34 
                 3.92 
               
               
                 Control 
                 14 
                 1.25 
                 0.88 
                 1.15 
                 1.26 
                 2.12 
                 1.64 
                 0.98 
                 1.36 
                 1.5 
                 2.12 
               
               
                 Control 
                 15 
                 1.14 
                 0.87 
                 1.16 
                 1.25 
                 4.57 
                 1.53 
                 1.02 
                 1.67 
                 1.7 
                 1.53 
               
               
                 LLLI 
                 16 
                 1.04 
                 0.9 
                 0.93 
                 1.03 
                 3.9 
                 1.28 
                 0.95 
                 1.03 
                 1.21 
                 6.28 
               
               
                 LLLI 
                 17 
                 1.05 
                 0.88 
                 1.02 
                 1.11 
                 2.99 
                 1.28 
                 0.91 
                 1.1 
                 1.3 
                 4.8 
               
               
                 LLLI 
                 18 
                 1.15 
                 0.9 
                 1.02 
                 1.18 
                 3.35 
                 1.61 
                 0.94 
                 1.53 
                 1.6 
                 2.19 
               
               
                 LLLI 
                 19 
                 1.17 
                 0.96 
                 1.11 
                 1.28 
                 2.05 
                 1.05 
                 0.78 
                 0.87 
                 1.04 
                 3.14 
               
               
                 LLLI 
                 20 
                 1.23 
                 0.92 
                 1.09 
                 1.21 
                 4.47 
                 1.57 
                 1.15 
                 1.51 
                 1.57 
                 2.89 
               
               
                 LLLI 
                 21 
                 1.04 
                 0.78 
                 1.04 
                 1.2 
                 3 
                 1.26 
                 1.04 
                 1.07 
                 1.25 
                 3.72 
               
               
                 LLLI 
                 22 
                 1 
                 0.89 
                 0.91 
                 1.05 
                 3.87 
                 1.3 
                 1.04 
                 1.23 
                 1.37 
                 3.31 
               
               
                 LLLI 
                 23 
                 1.08 
                 0.96 
                 1.12 
                 1.27 
                 4.04 
                 1.19 
                 1.02 
                 1.06 
                 1.16 
                 4.29 
               
               
                 LLLI 
                 24 
                 1.1 
                 0.85 
                 0.98 
                 1.15 
                 3.92 
                 1.36 
                 1.02 
                 1.16 
                 1.35 
                 3.98 
               
               
                 LLLI 
                 25 
                 1.19 
                 0.82 
                 1.04 
                 1.26 
                 4.56 
                 1.51 
                 1.13 
                 1.52 
                 1.61 
                 5.3 
               
               
                 LLLI 
                 26 
                 1.11 
                 0.88 
                 1.03 
                 1.18 
                 3.4 
                 1.38 
                 1.14 
                 1.37 
                 1.5 
                 4.64 
               
               
                 LLLI 
                 27 
                 1.17 
                 0.82 
                 1.03 
                 1.24 
                 4.01 
                 1.32 
                 1.08 
                 1.37 
                 1.5 
                 2.69 
               
               
                 LLLI 
                 28 
                 1.23 
                 0.8 
                 1.07 
                 1.24 
                 4.61 
                 1.15 
                 0.88 
                 1.22 
                 1.35 
                 4.56 
               
               
                   
               
               
                 LLLI = Low Level Laser Irradiation, MSR = Maximal Supra-Renal Diameter [mm], Ren = Inter Renal (internal control) Diameter [mm], Syst = Peak Systolic Diameter [mm], Dias = End Diastolic Diameter [mm], Veloc = Radial Wall Velocity [mm/sec], B = Baseline, E = Endpoint. TP = Technical Problem, 
               
               
                 *Outlier in the analysis of Radial Wall Velocity 
               
             
          
         
       
     
         [0080]    At the 4 week endpoint, 7 of 15 non-irradiated control mice had aneurysmal dilatation in the suprarenal aneurysm-prone segments of the aorta that had progressed to ≧50% expansion (maximal cross-sectional diameter [CSD]) over baseline, whereas none of the 13 low level laser irradiated mice had this degree of additional progression of dilatation (p=0.005 by Fisher&#39;s Exact Test) (Table 2, FIGS.  6 , 7 ). Likewise, when repeating this analysis for ≧40% expansion and ≧30% expansion, we found that the incidence, in mice treated with LLLI, was also significantly lower than the non-irradiated control mice (p=0.005 and p=0.003 respectively, by Fisher&#39;s Exact Test). 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Aneurysmal dilatation in the suprarenal aneurysm-prone segments of the 
               
               
                 aorta over baseline. 
               
             
          
           
               
                   
                 &gt;50% 
                 &gt;40% 
                 &gt;30% 
               
               
                   
                   
               
             
          
           
               
                   
                 Control 
                 7* 
                 9 
                 11 
               
               
                   
                 (n = 15) 
               
               
                   
                 LLLI 
                 0 
                 1 
                 2 
               
               
                   
                 (n = 13) 
               
               
                   
                 P †   
                 0.005 
                 0.005 
                 0.003 
               
               
                   
                   
               
               
                   
                 *Number of mice, 
               
               
                   
                   † by Fisher&#39;s Exact Test 
               
             
          
         
       
     
         [0081]    At baseline (12-13 weeks of age) there was no significant difference in the mean maximum CSD of the suprarenal segments (normalized individually to the maximal CSD of the adjacent, non-aneurysm-prone inter-renal segment) between control and LLLI treated animals (ratio of suprarenal/renal CSD, control-vs-LLLI=1.32±0.11-vs-1.29±0.13, p=0.5 by unpaired, 2-tailed t-test) ( FIG. 8 ). 
         [0082]    In the non-irradiated mice, the mean maximum CSD of the suprarenal aortic segments (normalized to the adjacent inter-renal aortic segments) increased significantly from baseline to 4 weeks (ratio of suprarenal/renal CSD, baseline-vs-4 weeks: 1.32±0.11-vs-1.82±0.39, p=0.0002 by paired, 2-tailed t-tests). However, in animals treated with LLLI, the maximum CSD of the suprarenal segments did not increase significantly from baseline to 4 weeks (mean of ratios of suprarenal/renal CSD, baseline vs 4 weeks: 1.29±0.13-vs-1.32±0.14, p=0.49 by paired, 2-tailed t-test). 
         [0083]    Direct comparisons at the 4 week endpoint between the suprarenal segments of LLLI and non-irradiated animals (normalized individually to inter-renal control segments) showed a highly significant attenuating effect of LLLI on aneurysm progression in this model (mean of ratios of suprarenal/renal CSD, LLLI-vs-non-irradiated: p=0.0002 by unpaired, 2-tailed t-test). 
         [0084]    These results show an overall 94% reduction in maximum CSD of the suprarenal aneurysm-prone segments compared to baseline in the LLLI treated mice in this model. 
         [0085]    Analysis of the M-mode data ( FIG. 9 , Table 3) showed that the mean diastolic diameter and the mean systolic diameter were significantly higher in the control animals compared to LLLI treated animals at the 4 week endpoint. In the non-treated control mice, the mean pulse diameter (PD) (normalized to systole) of the suprarenal aneurysm-prone aortic segments 4 weeks after angiotensin infusion was significantly lower than the mean PD at baseline. However, in the LLLI treated mice, the mean PD at 4 weeks was not significantly different from baseline. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 M-Mode Ultrasonographic Measurements 
               
             
          
           
               
                   
                   
                   
                 LLLI vs Control at 
               
               
                   
                 Control 
                 LLLI 
                 4 weeks: 
               
             
          
           
               
                   
                 Baseline 
                 4 weeks 
                 Baseline 
                 4 weeks 
                 p-value 
               
               
                   
                   
               
             
          
           
               
                 CSD in Diastole [mm] 
                 1.10 ± 0.08 
                 1.56 ± 0.35† 
                 1.03 ± 0.06 
                 1.23 ± 0.21** 
                 0.007 
               
               
                 CSD in Systole [mm] 
                 1.24 ± 0.07 
                 1.68 ± 0.31† 
                 1.18 ± 0.08 
                 1.37 ± 0.18** 
                 0.005 
               
               
                 PD 
                 0.11 ± 0.02 
                 0.07 ± 0.05* 
                 0.13 ± 0.03 
                 0.10 ± 0.04 
                 NS 
               
               
                 RWV [mm/sec] 
                 3.64 ± 0.89 
                 2.34 ± 1.20** 
                 3.71 ± 0.73 
                 3.98 ± 1.15 
                 0.002 
               
               
                   
               
               
                 All parameters are expressed as means ± SD. 
               
               
                 Comparisons between measurements at baseline and at the 4 week endpoint were performed by paired, 2-tailed t-test with Bonferroni correction for multiple comparisons. 
               
               
                 Comparisons between control and LLLI mice at the 4 week endpoint were performed by unpaired, 2 tailed t-test with Bonferroni correction. 
               
               
                 Baseline vs 4 weeks: 
               
               
                 *p &lt; 0.05; 
               
               
                 **p &lt; 0.01; 
               
               
                 †p &lt; 0.001. 
               
               
                 CSD = Cross Sectional Diameter, 
               
               
                 PD = pulse diameter (CSD in Systole − CSD in Diastole) normalized to CSD in systole, 
               
               
                 RWV = Radial Wall Velocity 
               
             
          
         
       
     
         [0086]    When considering individual mice, at the 4 week endpoint, 4 of 14 non-irradiated control mice had more than 75% reduction in the pulse diameter (normalized to maximal diameter in systole) over baseline; whereas none of the 13 low level laser irradiated mice had this degree of reduction in PD (p=0.057 by Fisher&#39;s Exact Test). 
         [0087]    The mean maximal radial wall velocity (RWV) ( FIG. 10 , Table 3) of the control group was significantly lower at 4 weeks than at baseline, but no such difference in RWV was found between 4 weeks and baseline in the LLLI treated mice. However, the mean RWV at 4 weeks was significantly greater in LLL irradiated compared to the non-irradiated animals. Moreover, when considering individual mice, at the 4 week endpoint, 6 of 13 non-irradiated control mice had more than 50% reduction in the maximal RWV over baseline, whereas none of the 13 low level laser irradiated mice had this degree of reduction of RWV (p=0.007 by Fisher&#39;s Exact Test). 
       DISCUSSION 
       [0088]    We have shown that LLLI limits the progression of aneurysmal dilatation in the suprarenal aneurysm-prone segment of the abdominal aorta in angiotensin-II infused apolipoprotein E-deficient mice. 
         [0089]    Whereas the higher power lasers used clinically for surgical excision and ablation convert photon energy into heat, low level lasers cause only minor temperature elevations with the usual energy densities ranging between 0.1 and 4 Joules/cm2. A variety of studies have suggested that these low energy photons are absorbed in the chromophores of the respiratory chain of the mitochondria. Studies by one of us (LG) have shown that this photon absorption apparently increases mitochondrial membrane potential. The latter is associated with an increase in the ATP energy store of the cell. This appears to represent a fundamental mechanism underlying the observed photomodulatory effects of LLLI. 
         [0090]    Abdominal aortic aneurysm (AAA) is present in 6-10% of the population over the age of 65. Current forms of treatment are based on either open surgical repair with grafts or endovascular repair by large membrane-covered stents. Both techniques have major side effects with potentially life-threatening consequences emphasizing the importance of developing alternative therapeutic strategies, such as that presented in the current study, that target pathogenetic mechanisms of progression and rupture. 
         [0091]    The angiotensin II-infused apolipoprotein E-deficient mouse model, developed by Daugherty and colleagues, shows important similarities to human AAA pathology. These include degradation of the elastic tissue associated with marked inflammatory cell infiltration and disruption of the musculo-elastic lamellar structure of the media including medial dissection. Similar changes have been detected in the elastase model of aneurysm and in the periarterial calcium chloride model developed in this laboratory. In the mouse angiotensin infusion model, these histological changes are usually found before the development of more advanced proliferative atherosclerotic lesions at these sites. However, AAA in humans, most commonly found in the infrarenal position, is usually diagnosed in a vessel that already has severe atherosclerotic changes in the wall. Nonetheless, marked inflammatory cell infiltration associated with disruption of the musculo-elastic architecture of the media is a major underlying histopathological process common to AAA in both animal models and man. 
         [0092]    Measurements obtained by femoral artery catheter and the tail cuff method confirmed that angiotensin II infusion did not increase blood pressure in this model, and hence the suprarenal aneurysms, and the associated wall changes are considered to occur independently of this parameter. 
         [0093]    High frequency ultrasonography (0.01 mm resolution) used in the current study was designed specifically for non-invasive microimaging in mice. Previous studies in the same mouse model showed a high correlation with direct post-mortem measurements of the outer diameter of the aorta obtained by digital photography and a very high correlation with morphometric measurements of H&amp;E stained histological sections (r=0.99). The measurements were also shown to have relatively small intra- and inter-individual variance. These studies support the accuracy and reproducibility of non-invasive high resolution ultrasound monitoring of the dimensions of AAA in living mice including the effects of investigative manipulations and treatment regimens over time. Histology will be necessary to study effects of LLLI on cell and tissue morphology and pathobio logy in this mouse model. However, the current study was designed to establish the effect of LLLI on aneurysm progression in vivo without the need for corrections of measurements for tissue shrinkage, embedding misalignment, or other perfusion fixation and preparation-related deformations of the arterial wall which confound accurate evaluation of wall shape by histopathology. 
         [0094]    We have shown that, in addition to a marked reduction in the mean maximum diameter of the supra-renal aortic segments of LLLI treated versus non-treated control aortas, the number of individual animals that developed aneurysmatic dilatation with greater than 50% increase in maximum CSD over baseline was significantly lower in the laser treated group. This degree of maximum diameter increase over baseline (or adjacent control segment) has been considered to be the accepted increment required for classification as a significant aneurysmal dilatation. 
         [0095]    Absolute measurements of cross-sectional diameter of the aorta can be considered sufficient for assessment of changes in aneurysmal dilatation from baseline to endpoint provided that both measurements are made in the same animal. However, when comparing the degree of aneurysmal dilatation in treated versus non-treated animals, use of absolute measurements alone fails to consider possible anatomical differences in vessel wall size between animals. Thus, in the current study, comparisons between treated and non-treated animals were be performed after normalizing the diameter measurement of the suprarenal aneurysm-prone segment to that of the adjacent, non-aneurysm-prone, non-dilated, internal control, inter-renal segment whose aortic diameter has been shown not to change over 28 days in this model. 
         [0096]    Analysis of M-mode data showed that the mean pulse diameter of the suprarenal aneurysmatic segment of non-treated control mice decreased from baseline to the 4 week endpoint. However, this was less pronounced in the LLLI treated animals, and the number of individual mice with significant reduction in PD was somewhat less (p=0.057). Reduced PD is a reduction in the difference between the arterial wall diameter of the affected segment in systole and that in diastole. This occurs in situations of arterial wall weakening and/or reduced wall elasticity leading to reduced contractility such as that associated with aneurysmal dilatation. This is also consistent with data accumulated from a variety of studies including from our laboratory which have identified marked changes in matrix protein expression, secretion, and degradation in this and other models of aneurysm formation. 
         [0097]    From M-mode data we also found a significantly lower mean maximal radial wall velocity in control mice at the 4 week endpoint than that measured in the LLLI treated mice, and a significantly greater number of control mice with more than 50% reduction in this parameter as compared to the LLL treated mice. Maximal RWV is the first derivative, or slope, of the aortic diameter over time. Reduction in the maximal RWV occurs with a decrease in the speed of the wall motility during the cardiac cycle. This phenomenon presents as changes in the echogenic texture of the vessel wall. Such changes are seen in cases of increased inflammatory cell infiltration that accompany changes in visco-elastic behavior of the arterial wall. That mice treated with LLLI in the current study showed significantly less reduction in RWV than non-treated controls is consistent with our in vitro findings of the effects of this modality on expression and secretion of inflammatory chemokines and cytokines, the effects on cell proliferation and matrix protein secretion, and the known empiric effects on a variety of clinical entities where inflammation is a major pathogenetic substrate. 
         [0098]    In conclusion, we have shown that LLLI significantly attenuates aneurysm formation in the angiotensin II-infused apolipoprotein E-deficient mouse. These studies, when considered together with previously reported in vitro studies, appear to provide strong support for initiation of studies in large animals as the next step toward testing the applicability of this technology to the human interventional setting. 
         [0099]    It will be apparent from the foregoing that while particular forms of the invention have been illustrated and described, various modifications can be made without departing from the spirit and scope of the invention. Accordingly, it is not intended that the invention be limited.