Technologies for Detection and Therapy of Vascular Plaques
An intravascular beta ray detection probe offers 3 main advantages over conventional PET imaging:
1) The resolution of the probe is significantly better than PET (2 vs. 6 mm).
2) Unlike with PET, the intravascular detection of short-range positrons is not affected by myocardial uptake of FDG. This is attributed to the fact that the beta probe detects beta particles (which travel less than 2 mm), and therefore, myocardium-derived particles do not reach the probe. On the other hand, PET detects annihilation photons, which traverse many centimeters through tissue.
3) An intravascular detector enables precise localization of VP during the same sitting as diagnostic coronary angiography. This enables the local delivery of plaque-stabilizing therapy in a way that non-invasive techniques do not.
We employed a PMT-optical fiber based beta-ray detector probe to examine the feasibility of intravascular detection. This early prototype of a flexible beta probe had a diameter of 1.6 mm and length of 40 cm. This probe is selectively more sensitive to positrons than gamma rays or annihilation photons. To construct this probe, a 1 mm diameter, 2 mm long plastic scintillator is optically connected to a PMT via a 1 mm diameter, 40 cm long optical fiber, and was covered by aluminized Mylar (thickness = 100 microns) acting as a reflector of the scintillation light. A computerized data acquisition system is used to collect and display the counts. The efficiency of the probe, measured by placing a point source of F-18 in touch with its sensitive tip, is only 0.2%. Our preliminary testing of the novel detector that we are proposing in this project demonstrated significant improvement in efficiency (so far we have achieved 15% efficiency) for a catheter of 160 cm length (see below.)
Flexible radiation detection beta probe
To test this early prototype and prove the concept, in the year 2002 our collaborators at MGH used an animal model. Atherosclerotic lesions were induced in New Zealand rabbits with a balloon injury to the infradiaphragmatic aorta followed by a high cholesterol diet. At 10 weeks, 37 MBq/kg FDG was administered to 4 rabbits with atherosclerotic lesions as well as to 3 control rabbits. 3-4 hours after FDG, the rabbits were sacrificed, and aortas removed as a single segment. The above mentioned flexible beta probe, was inserted into the aortae. Measurements were made in triplicate, (at 2 s/measurement), at sites of grossly visible plaque and at non-injured sites in the cholesterol fed rabbits, as well as in corresponding areas in the control aorta. The queried aortic segments were then excised and examined using standard well counting. Activity determined by the catheter correlated with well counting measurements, (r=0.89, P<0.001). Moreover, atherosclerotic plaques were readily distinguished from non-injured regions by the beta probe, (11.9±2.1 [n=9, range 9.7-15.3] vs. 4.8±1.9 [n=14, range 1.3-7.3], cps in atherosclerotic vs control regions, P<0.001).
Intravascular Beta Probe counts for VP and non-VP.
This animal study demonstrated that Atheron's intra-vascular beta probe, together with FDG, has promise for the in vivo detection of vulnerable plaques. But to be practical in humans it should have higher sensitivity, better flexibility, and a length of at least 160 cm.