Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis.

UNLABELLED: Balloon catheters filled with liquid radioisotopes provide excellent dose homogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled balloons may be improved once positron emitters with half-lives below 2 h are used instead of the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer half-life of at least 17 h. METHODS: To support this concept, the suitability of 18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4 min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a series of phantom experiments using Gafchromic film. Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with gamma-radiation emitted by 137Cs. To characterize the remaining risk, we estimated radiotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with 188Re. RESULTS: Half-dose depth of tissue penetration measured in phantom experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for 15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation (68Ga) induced dose-dependent inhibition of proliferation with complete proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4 Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/- 0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ doses were generally below 50 mSv/1.85 GBq for all investigated positron emitters. The same dose estimates for 188Re were 6-20 fold higher. CONCLUSION: Among the studied radioisotopes, 68Ga is the most attractive source for liquid-filled balloons because of its convenient half-life, sufficient positron energy (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability from a radioisotope generator. The safety profile for 68Ga is significantly better than that of 188Re, which suggests this radioisotope should be evaluated further in preclinical studies.

Liquid-filled balloon brachytherapy using (68)Ga is effective and safe because of the short 68-minute half-life: results of a feasibility study in the porcine coronary overstretch model.

BACKGROUND: Liquid-filled balloons for coronary brachytherapy provide significant advantages over solid sources in dose homogeneity but carry the risk of life-threatening radiointoxication after balloon rupture and laboratory contamination in case of a spill. We hypothesized that the positron emitter (68)Ga, with a half-life of only 68 minutes, was well suited to overcome these safety obstacles while providing full therapeutic efficacy. METHODS AND RESULTS: The feasibility, efficacy, and safety of (68)Ga liquid-filled balloon brachytherapy were investigated in the porcine coronary overstretch model. Four groups of 5 balloon-induced coronary lesions were irradiated with 8, 12, 16, and 24 Gy targeted to the adventitia. Ten unirradiated lesions served as controls. Segments treated with 16 or 24 Gy exhibited marked suppression of neointimal proliferation at 28-day follow-up, with quantitative parameters of intraluminal proliferation reduced to <20%. This beneficial effect was not compromised by untoward edge effects. Uninjured but irradiated vessels did not show histological signs of radiation damage. The (68)Ga whole-body dose due to balloon rupture was estimated to be 5 rem/50 mCi treatment activity and compared favorably with that of (188)Re (78 rem/50 mCi). CONCLUSIONS: (68)Ga positron radiation suppresses neointimal proliferation at doses of 16 and 24 Gy. This biological efficacy, coupled with the attractive safety profile, suggests the selection of (68)Ga as an attractive isotope for liquid-filled balloon brachytherapy.

A new approach to the interpolation of sampled data.

A new class of interpolation kernels that are locally compact in signal space and "almost band-limited" in Fourier space is presented. The kernels are easy to calculate and lend themselves to problems in which the kernels must be analytically manipulated with other operations or operators such as convolutions and projection integrals. The interpolation kernels are comprised of a linear sum of a Gaussian function and its second derivative (and, when extended to higher order, its higher even derivatives). A numerical Gaussian quadrature method is derived that can be used with integrals involving the kernels that cannot be analytically evaluated. Potential extensions to higher order implementations of the kernels are discussed and examined. The emphasis of the manuscript is on the simplicity of the interpolation kernel and some of its mathematical properties.

Photoacoustic ultrasound (PAUS)--reconstruction tomography.

The theoretical underpinnings of photoacoustic ultrasound (PAUS) reconstruction tomography are presented. A formal relationship between PAUS signals and the heterogeneous distribution of optical absorption within the object being investigated is developed. Based on this theory, a reconstruction approach, analogous to that used in x-ray computed tomography, is suggested. Initial experimental results suggest that this approach produces "reasonable" reconstructions for absorbers distributed within a narrow plane embedded within a highly scattering medium.

Initial experience with a radiology imaging network to newborn and intensive care units.

A digital image network has been installed in the James Whitcomb Riley Hospital for Children on the Indiana University Medical Center to create a limited all digital imaging system. The system is composed of commercial components, Philips/AT&T CommView system, (Philips Medical Systems, Shelton, CT; AT&T Bell Laboratories, West Long Beach, NJ) and connects an existing Philips Computed Radiology (PCR) system to two remote workstations that reside in the intensive care unit and the newborn nursery. The purpose of the system is to display images obtained from the PCR system on the remote workstations for direct viewing by referring clinicians, and to reduce many of their visits to the radiology reading room three floors away. The design criteria includes the ability to centrally control all image management functions on the remote workstations to relieve the clinicians from any image management tasks except for recalling patient images. The principal components of the system are the Philips PCR system, the acquisition module (AM), and the PCR interface to the Data Management Module (DMM). Connected to the DMM are an Enhanced Graphics Display Workstation (EGDW), an optical disk drive, and a network gateway to an ethernet link. The ethernet network is the connection to the two Results Viewing Stations (RVS) and both RVSs are approximately 100 m from the gateway. The DMM acts as an image file server and an image archive device. The DMM manages the image data base and can load images to the EGDW and the two RVSs. The system has met the initial design specifications and can successfully capture images from the PCR and direct them to the RVSs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of age and menopause on vertebral bone density.

Vertebral bone density was assessed with dual photon absorptiometry in 280 white females, aged 19-87, without symptoms of osteoporosis. Those who had not experienced a menstrual period for at least one year were classified as postmenopausal, and those menstruating normally were deemed premenopausal. The remainder were considered perimenopausal. Regression links were fit: (1) to the entire data set, (2) to two groups by age (less than 50, 50+), (3) to three groups by age (less than 40, 40-54, 55+) and (4) to three groups by menopausal status. Only that regression which considered menopausal status had a significantly better fit than the simple linear model with slopes of +0.04% per year for the premenopausal (ns, different from zero), -1.8% per year for the perimenopausal (P less than 0.05) and -0.6% per year for the postmenopausal (P less than 0.05). These data suggest that the loss of trabecular bone is accelerated around the time of the onset of menopause, and slows somewhat thereafter, although continuing to be significant. However, the findings of this study are based on cross-sectional data, and there remains a need for prospective studies of vertebral bone around the time of menopause.

Uniformity correction for SPECT using a mapped cobalt-57 sheet source.

As little as 1% nonuniformity of the scintillation camera can produce disturbing artifacts in SPECT images. To correct for nonuniformity, acquired images must be divided by the flood-field image of a uniform sheet source. The refillable 99mTc sheet source requires meticulous preparation before each use, and is subject to spillage. We propose the use of a permanent 57Co solid sheet source in conjunction with a map of the radioactivity distribution in the source. The flood-field image of the cobalt source is converted by the map into the equivalent of a flood-field image of an almost perfectly uniform source. An accurate and reproducible method is described for generating a map of the cobalt sheet source from images of it made in multiple positions with the scintillation camera. The mapping process is independent of sensitivity variations across the face of the camera.

Functional renal imaging through factor analysis.

Functional images tend to be noisy, since they are formed from parameter values estimated from noisy time-activity curves. Factor analysis provides a rapid method for fitting smooth curves to these noisy curves. Noise in functional images is reduced by estimating parameter values from the smooth curves. The method is illustrated for three parameters: TMAX (time to maximum value), RISE (increase from first to maximum value), and RISMX (maximum increase between successive values). When curve-fitting through factor analysis is used to generate functional renal images from clinical studies or to estimate parameter values for simulated noisy renogram curves, noise is reduced for the TMAX and RISMX parameters and accuracy is improved for the RISE parameter.

An automated method for the alignment of image pairs.

The computer comparison of two images of the same organ requires proper alignment of the images before further computer processing. This alignment can be achieved by (a) fixing patient position during the study, (b) alignment methods using analytical transformations, or (c) operator interaction. We propose an automated method based upon the cross-correlation between projections of the images. With fast Fourier transforms, the algorithm becomes computationally cheap.