Purpose: To assess the variation of Hounsfield units (HU) when using different CT scanning parameters. The effect of HU‐to‐electron density (ED) table on the accuracy of dose calculations was evaluated. Methods: A CIRS (model 62) phantom was used for all the tests. Various kVp, field‐of‐view(FOV), reconstruction algorithms with contribution of adaptive statistical iterative reconstruction(ASiR™) (0‐80%) were applied during the scanning process(GE lightspeed CT simulator). HU for each insert was measured. A HU‐ED table was acquired for Philips PET/CT scanner as well. A phantom and clinical cases were selected for dosimetric comparisons using different HU‐ED tables. Results: No significant difference in HU for low electron density material was observed regardless the scanning parameters. The dependency of HU on tube voltage and FOV was observed for bone‐equivalent materials. HU for dense bone scanned with 80kVp was 39.4% higher than HU with 120kVp. HU with small FOV relative to large FOV was 11.9% higher for trabecular bone. The maximum deviation was observed for bone‐equivalent material when the bone algorithm, producing a 6.2% change in HU, or 80% of ASiR™ contribution, were applied; however, the difference in HU was still within the standard deviation. The difference in HU between two scanners was less than the SD observed on GE CT simulator, except for liver‐and bone‐equivalent materials. Using a HU‐ED table with the worse case scenario (80kVp, bone reconstruction with 80% ASiR™), it was shown that the deviation was within 1% for phantom studies and −7.4%−2.7% for clinical cases. The maximum of 5.9% deviation was observed when calculated with a table from the different scanner. Conclusion: The maximum deviation in HU was observed for bone‐equivalent materials when low kVp was applied. Use of a wrong HU‐ED table could introduce −7.4%−2.7% dosimetric error at certain regions of interest.

PURPOSE:Human observations provide rich soil for making hypotheses, but good animal models are essential for understanding the disease and to test treatment modalities. Currently, there is no standard animal model of vulnerable plaque; therefore, the purpose of this study is to develop a pathophysiologically relevant vulnerable plaque model. METHODS:New Zealand White rabbits were fed with 1% hypercholesterolemic (HC) diet for 7 days, followed by balloon denudation of both the iliac arteries, and continued on 1% HC diet. Four weeks later, in 12 rabbits one of the iliac arteries was radiated (192-Ir, 15 Gy), and in five rabbits both the iliac arteries were sham treated. Following that, rabbits were fed with 0.15% HC diet. Four weeks later, arteries were processed for histomorphometry or immunohistochemistry. RESULTS:Serum cholesterol levels were similar in all the groups. In radiated arteries, plaque area was significantly larger (32% larger then in sham). Macrophage-positive area in radiated arteries was 2.4 times greater than the macrophage-positive area in the nonradiated arteries. The area positive for macrophages is also positive for metalloproteinases (MMP)-1. The extent of alpha-actin positive area was significantly less (2.3-fold) in radiated arteries. CONCLUSION:The atherosclerotic plaque developed in the current model is predominantly composed of macrophages expressing metalloproteinases with few smooth muscle cells (SMC)--a characteristic of vulnerable plaque. The animal model presented in this study can elucidate at least part of the mechanism of plaque vulnerability and could be used to test treatment modalities to test plaque stability.

Background: The effects of overlapping β-emitter sources on the treatment of in-stent restenosis (ISR) lesions as a result of manual stepping are unknown. Methods and results: In the BETA WRIST (Beta Washington Radiation for In-stent Restenosis Trial), 17 out of the 50 patients who received radiation treatment had diffuse ISR in native coronaries that required manual stepping of the β-emitter (90Y) source in order to cover the lesion and the edges. Fourteen of those patients received radiation with an overlap of up to 3 mm in the middle of the stented segment. The prescribed dose was 20.6 Gy to a distance of 1.0 mm from the surface of the inflated balloon, and the calculated dose to the vessel wall at the overlapped area did not exceed 75 Gy. There was no difference in late total occlusion (7.1% vs. 9.0%, P=NS) and target lesion revascularization (28.5% vs. 27.2%, P=NS) between patients with stepping and those without stepping. At 6 months, there was no evidence of perforation or aneurysm at the overlapped segments. Quantitative coronary angiographic (QCA) analysis revealed significantly reduced late loss in the overlapped segment compared to the adjacent segment (P=.04). Serial (postradiation vs. follow-up) IVUS measurement showed larger mean lumen cross-sectional area (CSA) (P=.0035) and smaller mean intimal hyperplasia (IH) CSA (P=.0010) in the overlapped segment compared to the adjacent segment. Conclusion: Manual stepping of β-emitter source with a short overlapped segment is safe for diffuse ISR. Further increase in lumen dimension and reduction in IH formation are observed at the overlapped segment.

To study the safety and efficacy of intracoronary gamma radiation delivered via a new high-activity 192Ir source wire for the treatment of in-stent restenosis. In-stent restenosis results from neointimal tissue proliferation especially in its diffused form and presents a therapeutic challenge. Gamma radiation has been shown to decrease neointima formation within stents in animal models and in initial clinical trials. A total of 26 patients with in-stent restenosis underwent successful intervention and was treated with open-label 192Ir using a high-activity line source. The specific activity of the source wire was 372±51 mCi, and the dwell time was 10.8±1.9 min. Primary endpoints were freedom from death, myocardial infraction (MI), and repeat target lesion revascularization (TLR) at 6 months. Secondary endpoints included angiographic restenosis and intravascular ultrasound (IVUS) neointimal hyperplasia. Procedural success was high (96.2%), and in-hospital and 30-day complications were low with no deaths, MI, or requirement for repeat revascularization. At 6 months, event-free survival was 85%: one patient required repeat PTCA, one underwent bypass surgery, and two had an MI. Baseline lesion length measured 15.77 mm. Follow-up angiography was available in 21/25 (84%) patients. The binary restenosis rates were 19.0% (4/21) in-stent and 23.8% (5/21) in-lesion. Follow-up IVUS was available in 20/25 patients. There was no increase in intimal hyperplasia from postintervention to follow-up (3.11.8 vs. 3.41.8 mm2; P=.32). Eight patients had a reduction of neointimal intimal tissue at follow-up. These results indicate that intracoronary gamma radiation with the Angiorad source wire is safe and effective in preventing in-stent restenosis.

Background: Intracoronary radiation (IR) studies have shown reduction of neointima formation (NF). Extrapolation of animal studies with beta-radiation to clinical trials have shown variable results, which may be related to dosimetry, centering issues, and/or shielding of beta-rays by the stent metal. We examined the effect of yttrium-90 (90Y), a pure beta-emitter delivered via an automatic afterloader to a centering catheter, on the inhibition of NF in balloon-injured (BI) porcine coronary arteries as well as in arteries receiving 90Y either prior to or following stent implantation (SI).Methods: Twenty-three swine (44 coronary arteries) were studied. In the first study, IR (18 Gy at 1.2 mm from the balloon surface) was administered in 17 arteries following BI, while eight control arteries were subjected to BI only. In the second study, 10 swine (19 coronary arteries) underwent SI. IR (18 Gy) was administered in six arteries before and in eight arteries after SI, while five control arteries received SI only. The animals were sacrificed 2 weeks after BI and 4 weeks after SI. Their coronaries were perfusion fixed and stained, and vessel parameters (intimal area [IA] and medial fracture length [FL]) were analyzed by computer-aided histomorphometry.Results: Arteries subjected to IR following BI had less NF compared to controls (IA/FL=0.14+/-0.2 mm vs. 0.49+/-0.2 mm; P=0.003). IA was reduced significantly in the arteries receiving radiation before and after SI compared to controls (0.92+/-0.98 and 0.00+/-0/00 vs. 2.72+/-1.2 mm(2); P=0.014), despite similar SI in all groups.Conclusions: IR with 90Y delivered via a centering catheter is safe and effective with complete and homogenous inhibition of NF in the context of BI or SI in the porcine coronary model.

Background: Restenosis is a consequence of both neointimal hyperplasia and vessel remodeling. Prior studies have shown that intracoronary radiation (IR) prevents neointima accumulation, but its contribution to vessel remodeling is unknown. The purpose of this study was to evaluate the effect of IR on differential vascular remodeling after balloon angioplasty in porcine coronary arteries. Methods: A total of 20 juvenile swine (30 coronary arteries) were subjected to overstretch balloon injury (BI) followed by IR with either β- or γ-radiation (90Y or 192Ir). After 2 weeks following treatment, serial tissue sections were perfusion fixed and stained by hematoxylin and eosin (H&E), Verhoeff von Giesson (VVG), or Masson Trichrome. Adventitial area (AA), lumen area (LA), vessel area (VA), intimal area (IA), and IA corrected for medial fracture length (IA/FL) were quantified by digital image analysis. The vessel circumference was divided into two regions containing (1) the undisrupted region (UReg) with the undisrupted arc of media and internal elastic lamina (IEL) and (2) the disrupted region (DReg) with the disrupted arc between the medial tears. Quantitative regional analysis was performed by (1) measuring the IEL to define the UReg, (2) calculating the area of the UReg with the perimeter value derived from measurement of the IEL, and (3) calculating the DReg as follows: LA+IA−UReg. Immunohistochemical smooth muscle cell α-actin and Masson Trichrome were quantified by digital image analysis. Results: The IA/FL was significantly smaller following treatment with 90Y or 192Ir vs. control (P<.01). A smaller AA was obtained following IR with both β- and γ-sources vs. control (P<.01). The UReg calculation was smaller in the irradiated arteries as compared to control (β: 2.3±0.4 mm2, γ: 2.1±0.5 mm2, P<.01 vs. control; control: 3.6±0.7 mm2). In contrast, the DReg was increased following IR, as demonstrated by the FL and the calculated area of the injured segment (control: 2.7±0.5 mm2; β: 5.5±1.1 mm2, γ: 5.5±1.1 mm2, P<.01 vs. control). Adventitial α-actin positive cell density (CD) was decreased after IR; however, the collagen density was similar. In contrast, the neointimal collagen density in the injured segment was significantly decreased following IR. Conclusion: We consider that the global arterial remodeling after IR is a heterogeneous process that includes the absence of retraction in an UReg and a positive remodeling in the DReg as shown in the porcine coronary model. These changes in adventitia and neointima appear to contribute to differential vascular remodeling caused by IR in injured vessels.

Purpose. Recurrence of obstructive coronary arterial lesions (restenosis) after angioplasty remains a significant clinical problem. Ionizing radiation, at doses >10 Gy administered locally to the angioplasty site, has been shown to inhibit restenosis in porcine coronary arteries, but lower doses are ineffective. Methods that will allow delivery of lower doses of radiation while retaining the antirestenotic efficacy observed at the higher doses are desirable. Hypoxic cells are known to be radioresistant; accordingly, we hypothesized that increasing blood oxygenation through the use of the TherOx Aqueous Oxygen™ system would lower the doses of endovascular radiation required for the prevention of restenosis.

Restenosis is a common complication of percutaneous transluminal coronary angioplasty. Recent studies have demonstrated a striking reduction in the neointimal hyperplasia characteristic of restenosis following intracoronary radiation (IR), but the mechanisms by which radiation reduces neointima formation following balloon overstretch injury are not elucidated fully. In addition to direct antimitotic effects mediated via oxygen free radicals, ionizing radiation can induce the expression of numerous genes and thereby mediate indirect effects. Additionally, IR prevents restenosis at the cost of decreased healing and increased thrombosis, and we suggest that these adverse reactions can be modulated by adjunct pharmacology or gene-based strategies. This review discusses several genes and proteins modulated by radiation in the context of arterial injury, and their possible therapeutic relevance.

Background. In-stent restenosis (ISR) is a limitation of intracoronary stent implantation. In animal models and clinical trials, ionizing radiation has been shown to decrease in-stent neointimal formation.

Local delivery of high-energy ionizing radiation by using 3 or 3 emitters to injured vessels demonstrated inhibition of cell proliferation (CP) and neointima formation. Low-energy ('soft') X-radiation (LEXR) offers logistic and safety advantages over the use of disposable radioisotopes. This study evaluated the efficacy of LEXR in penetration and inhibition of CP at doses similar to those prescribed for the use of radioisotopes for prevention of restenosis. Serial measurements in an ion chamber detected the attenuation of LEXR using potentials of 17 and 40 kV at a distance of 17 cm of air through 0-10 mm depths of serum-containing tissue culture medium. The effect of inhibition on CP was determined by exposing V79 fibroblasts to a potential of 17 kV in order to deliver a prescribed dose of 13 Gy at a dose rate of 2.17 Gy/min to the surface of the cells. Complete inhibition of CP at a height of 0.00 mm occurred with 13 Gy; however, a 50% attenuation of the dose was measured at a medium depth of 1.22 mm and was associated with a reduction of 60% of the CP. LEXR demonstrated an ability to inhibit CP at doses equivalent to those used in techniques involving 3 and 3 irradiation. Under such conditions, the dose gradient is too high, especially for large vessels. However, a catheter-based LEXR that could be inserted into the artery with the capability of varying effective energy would be ideal for intravascular applications.