Assessing radiation-induced carotid artery injury using ultrasound in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Radiotherapy (RT) can damage neck vessels in patients with head and neck cancer (HNC). This study investigated the early effects of RT on carotid artery, including the internal media thickness (IMT) and carotid plaques of the common carotid artery (CCA). MATERIALS AND METHODS: This study included 69 patients with HNC who underwent RT at the First Hospital of Jilin University from March 2017 to September 2022, and 69 healthy participants as controls. Color Doppler ultrasound (CDUS) of the carotid artery was used to measure the CCA IMT and plaques. RESULTS: Left CCA IMT increased from 0.60 mm (0.60, 0.70) before RT to 0.70 mm (0.60, 1.20) after RT (P < 0.0001). Right CCA IMT changed from 0.60 mm (0.60, 0.71) before RT to 0.60 mm (0.60, 1.10) after RT (P = 0.0002). CCA IMT was 0.60 mm (0.60, 0.70) and 0.80 mm (0.60, 1.20) in the ≤40 Gy and >40 Gy groups (P = 0.0004). The CCA plaques number increased significantly after RT on both the left and right sides (Pleft < 0.0001; Pright <0.0001). The CCA plaques volume increased from 0 mm3 (0, 11.35) and 0 mm3 (0, 8.55) before RT to 8.8 mm3 (0, 21.5) and 5.8 mm3 (0, 16.1) on the left and right sides. Correlation analysis revealed a correlation between CCA IMT and age (r = 0.283, P = 0.001), smoking status (r = 0.179, P = 0.020), and radiation dose (r = 0.188, P = 0.028). CONCLUSION: RT significantly increased CCA IMT, and the growth was related to the radiation dose. The number and volume of the CCA plaques also increased after RT.

Assessing radiation-induced carotid vasculopathy using ultrasound after unilateral irradiation: a cross-sectional study.

BACKGROUND: Increased head and neck cancer (HNC) survival requires attention to long-term treatment sequelae. Irradiated HNC survivors have a higher ischemic stroke risk. However, the pathophysiology of radiation-induced vasculopathy is unclear. Arterial stiffness could be a biomarker. This study examined alterations in intima-media thickness (IMT) and stiffness-related parameters, shear wave (SWV) and pulse wave velocity (PWV), in irradiated compared to control carotids in unilateral irradiated patients. METHODS: Twenty-six patients, median 40.5 years, 5-15 years after unilateral irradiation for head and neck neoplasms underwent a bilateral carotid ultrasound using an Aixplorer system with SL18-5 and SL10-2 probes. IMT, SWV, and PWV were assessed in the proximal, mid, and distal common (CCA) and internal carotid artery (ICA). Plaques were characterized with magnetic resonance imaging. Measurements were compared between irradiated and control sides, and radiation dose effects were explored. RESULTS: CCA-IMT was higher in irradiated than control carotids (0.54 [0.50-0.61] vs. 0.50 [0.44-0.54] mm, p = 0.001). For stiffness, only anterior mid-CCA and posterior ICA SWV were significantly higher in the irradiated side. A radiation dose-effect was only (weakly) apparent for PWV (R2: end-systolic = 0.067, begin-systolic = 0.155). Ultrasound measurements had good-excellent intra- and interobserver reproducibility. Plaques had similar characteristics but were more diffuse in the irradiated side. CONCLUSIONS: Increased CCA-IMT and SWV in some segments were seen in irradiated carotids. These alterations, even in young patients, mark the need for surveillance of radiation-induced vasculopathy. TRIAL REGISTRATION: clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04257968 ).

Irradiation Accelerates Plaque Formation and Cellular Senescence in Flow-Altered Carotid Arteries of Apolipoprotein E Knock-Out Mice.

Background Chronic inflammation through cellular senescence, known as the senescence-associated secretory phenotype, is a mechanism of various organ diseases, including atherosclerosis. Particularly, ionizing radiation (IR) contributes to cellular senescence by causing DNA damage. Although previous clinical studies have demonstrated that radiotherapy causes atherosclerosis as a long-term side effect, the detailed mechanism is unclear. This study was conducted to investigate the relationship between radiation-induced atherosclerosis and senescence-associated secretory phenotype in murine carotid arteries. Methods and Results Partial ligation of the left carotid artery branches in 9-week-old male apolipoprotein E-deficient mice was performed to induce atherosclerosis. The mice received total body irradiation at a dose of 6 Gy using gamma rays at 2 weeks post operation. We compared the samples collected 4 weeks after IR with unirradiated control samples. The IR and control groups presented pathologically progressive lesions in 90.9% and 72.3% of mice, respectively. Plaque volume, macrophage accumulation, and phenotype switching of vascular smooth muscle cells were advanced in the IR group. Irradiated samples showed increased persistent DNA damage response (53BP1 [p53 binding protein 1]), upregulated cyclin-dependent kinase inhibitors (p16INK4a and p21), and elevated inflammatory chemokines expression (monocyte chemotactic protein-1, keratinocyte-derived chemokine, and macrophage inflammatory protein 2). Conclusions IR promoted plaque growth in murine carotid arteries. Our findings support the possibility that senescence-associated secretory phenotype aggravates atherogenesis in irradiated artery. This mice model might contribute to mechanism elucidation of radiation-induced atherosclerosis.

Carotid Artery Stenosis after Radiation Therapy in a Patient with Lung Cancer: A Case Report and Literature Review.

We reported a case of carotid artery stenosis with stroke symptoms detected in a patient with lung cancer after radiotherapy. The patient was a 58-year-old male with a complaint of \"a single episode of temporary amaurosis in the right eye for 10 minutes". The clinical diagnosis at admission, after consideration of the patient's age, medical history, and auxiliary examination results, was as follows: lung cancer; right common carotid artery stenosis; left common carotid artery stenosis; left vertebral artery stenosis; and right subclavian artery occlusion with right subclavian steal syndrome (Grade 3). Carotid angioplasty and stenting (CAS) were subsequently performed. During the 6-month follow-up, we observed no episode of temporary vision loss or other signs of stroke. Clinicians should pay great attention to delayed radiation-induced carotid stenosis. It is recommended that patients with a history of radiotherapy should undergo regular color Doppler ultrasound examination of the cervical region to diagnose, prevent, and treat RICS in an expedient fashion. This approach should improve survival rate and quality of life.

Ultrasound Evaluation of Carotid Atherosclerosis in Post-Radiotherapy Nasopharyngeal Carcinoma Patients, Type 2 Diabetics, and Healthy Controls.

Purpose To comprehensively evaluate and compare the degree of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC) and in patients with type 2 diabetes mellitus (DM), and using healthy subjects as controls. Materials and Methods The present study recruited 69 post-RT NPC patients without conventional cardiovascular risk factors, 70 type 2 diabetic patients without previous RT, and 76 healthy controls without conventional cardiovascular risk factors and previous RT. For each participant, 5 carotid atherosclerotic parameters, namely carotid intima-media thickness (CIMT), carotid arterial stiffness (CAS), presence of carotid plaque, carotid plaque score, and presence of ≥ 50 % carotid stenosis, were assessed using ultrasonography. The differences in these carotid atherosclerotic parameters between study groups were compared using ANCOVA or logistic regression after the adjustment for age and gender. Multiple comparisons were corrected using the Benjamini-Hochberg false discovery rate. Results Post-RT NPC patients and type 2 diabetics had a significantly higher CIMT, CAS and carotid plaque burden compared to the healthy subjects (corrected P-value, Pcor < 0.05). In addition, carotid atherosclerosis in post-RT NPC patients tended to be more severe with significantly higher CAS and carotid plaque burden than that in type 2 diabetics (Pcor < 0.05). Conclusion Neck RT for NPC is an independent risk factor of carotid atherosclerosis, and radiation induces more severe carotid atherosclerosis in post-RT NPC patients. Thus, assessment of carotid atherosclerosis using ultrasonography may be necessary for these patients and should be indicated in the routine follow-up of NPC.

Endovascular recanalization of the common carotid artery in a patient with radio induced chronic occlusion.

Recanalization of chronic occlusion of the common carotid artery (CCA) in patients with a history of neck irradiation is challenging, both for vascular surgeons and interventional neuroradiologists. We describe a case of successful stenting of radio induced chronic occlusion of the right CCA in a 41-year-old patient with neurological deterioration and minor stroke due to cerebral hypoperfusion caused by concomitant bilateral arterial occlusions. Direct surgery and surgical bypass were considered contraindicated. The endovascular approach was successful and required multiple precautions during the procedure. We describe particular solutions, not used in day to day practice, that allowed us to carry out the endovascular treatment in this unusual situation.

Cardiovascular Consequences of Prostanoid I Receptor Deletion in Microsomal Prostaglandin E Synthase-1-Deficient Hyperlipidemic Mice.

BACKGROUND: Inhibitors of cyclooxygenase-2 alleviate pain and reduce fever and inflammation by suppressing the biosynthesis of prostacyclin (PGI2) and prostaglandin E2. However, suppression of these prostaglandins, particularly PGI2, by cyclooxygenase-2 inhibition or deletion of its I prostanoid receptor also predisposes to accelerated atherogenesis and thrombosis in mice. By contrast, deletion of microsomal prostaglandin E synthase 1 (mPGES-1) confers analgesia, attenuates atherogenesis, and fails to accelerate thrombogenesis, while suppressing prostaglandin E2, but increasing biosynthesis of PGI2. METHODS: To address the cardioprotective contribution of PGI2, we generated mice lacking the I prostanoid receptor together with mPges-1 on a hyperlipidemic background (low-density lipoprotein receptor knockouts). RESULTS: mPges-1 depletion modestly increased thrombogenesis, but this response was markedly further augmented by coincident deletion of the I prostanoid receptor (n=10-18). By contrast, deletion of the I prostanoid receptor had no effect on the attenuation of atherogenesis by mPGES-1 deletion in the low-density lipoprotein receptor knockout mice (n=17-21). CONCLUSIONS: Although suppression of prostaglandin E2 accounts for the protective effect of mPGES-1 deletion in atherosclerosis, augmentation of PGI2 is the dominant contributor to its favorable thrombogenic profile. The divergent effects on these prostaglandins suggest that inhibitors of mPGES-1 may be less likely to cause cardiovascular adverse effects than nonsteroidal anti-inflammatory drugs specific for inhibition of cyclooxygenase-2.

Contrast enhancement of carotid adventitial vasa vasorum as a biomarker of radiation-induced atherosclerosis.

PURPOSE: Abnormal proliferation of adventitial vasa vasorum (vv) occurs early at sites of atherosclerosis and is thought to be an early biomarker of vascular damage. Contrast-enhanced ultrasound (CEUS) can detect this process. Its usefulness in irradiated arteries as a measure of accelerated atherosclerosis is unknown. This study investigates contrast intensity in carotid adventitia as an early marker of radiation-induced damage in head and neck cancer (HNC) patients. MATERIALS/METHODS: Patients with HNC treated with a wedged-pair and matched neck technique or hemi-neck radiotherapy (RT) (unirradiated side as control) at least 2years previously were included. Patients had been prescribed a dose of at least 50Gy to the neck. CEUS was performed on both carotid arteries and a region of interest was selected in the adventitia of the far wall of both left and right distal common carotid arteries. Novel quantification software was used to compare the average intensity per pixel between irradiated and unirradiated arteries. RESULTS: 48 patients (34 males) with median age of 59.2years (interquartile range (IQR) 49.2-64.2) were included. The mean maximum point dose to the irradiated artery was 61.2Gy (IQR 52.6-61.8) and 1.1Gy (IQR 1.0-1.8Gy) to the unirradiated side. The median interval from RT was 59.4months (IQR 41-88.7). There was a significant difference in the mean (SD) contrast intensity per pixel on the irradiated side (1.1 (0.4)) versus 0.96 (0.34) on the unirradiated side (p=0.01). After attenuation correction, the difference in mean contrast intensity per pixel was still significant (1.4 (0.58) versus 1.2 (0.47) (p=0.02). Previous surgery or chemotherapy had no effect on the difference in contrast intensity between the 2 sides of the neck. Mean intensity per pixel did not correlate to traditional risk prediction models (carotid intima-medial thickness, QSTROKE score). CONCLUSIONS: Proliferation of vv is demonstrated by increased contrast intensity in irradiated carotid arteries. This may be a useful, independent biomarker of radiation-induced carotid atherosclerosis when used as a tool to quantify neovascularization.

Arterial Stiffness as a Biomarker of Radiation-Induced Carotid Atherosclerosis.

Arterial stiffness is thought to be a precursor to atherosclerosis. Conventional arterial stiffness parameters as potential biomarkers of radiation-induced damage were investigated. Patients with head and neck cancer treated with radiotherapy ≥2 years previously to one side of the neck were included. The unirradiated side was the internal control. Beta stiffness index (B) and elastic modulus (Ep) were used to assess arterial stiffness and were measured in proximal, mid, and distal common carotid artery (CCA) and compared with the corresponding unirradiated segments. Fifty patients (68% male; median age 58 years; interquartile range 50-62) were included. Mean ± standard deviation maximum doses to irradiated and unirradiated arteries were 53 ± 13 and 1.9 ± 3.7 Gy, respectively. Differences in B were not significant. Significant differences in Ep were demonstrated-proximal CCA: 1301 ± 1223 versus 801 ± 492 (P < .0001), mid CCA: 1064 ± 818 versus 935.5 ± 793 (P < .0001), and distal CCA: 1267 ± 1084 versus 775.3 ± 551.9 (P < .0001). Surgery had no impact on arterial stiffness. Arterial stiffness is increased in irradiated arteries, in keeping with radiation-induced damage. Prospective data may show an association between arterial stiffness and atherosclerosis in this setting.

Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND: Vascular abnormalities are the predominant histologic changes associated with radiation in nasopharyngeal carcinoma (NPC). This study examined if the duration after radiotherapy correlates with the progression of carotid intima-media thickness (IMT) and investigated its relationship with inflammatory markers. METHODS: One hundred and five NPC patients post-radiotherapy for more than one year and 25 healthy control subjects were examined by B-mode ultrasound for IMT measurement at the far wall of the common carotid artery (CCA). Surrogate markers including lipid profile, HbA1c, and high sensitive C-reactive protein (hs-CRP) were assessed. RESULTS: The IMT of CCA was significantly increased in NPC patients and carotid plaque was detected in 38 NPC patients (38/105, 36.2%). Significant risk factors for carotid plaques included age, duration after radiotherapy, and HbA1c levels. Age, duration after radiotherapy, hs-CRP, HbA1c, and platelet count positively correlated with IMT. The cut-off value of age and duration after radiotherapy for the presence of plaque was 52.5 years and 42.5 months, respectively. In NPC subjects, multiple linear regression analysis revealed that age, gender, duration after radiotherapy and platelet counts were independently associated with CCA IMT. After adjustments for age, gender and platelet counts, IMT increased in a linear manner with duration after radiotherapy. CONCLUSIONS: Radiation-induced vasculopathy is a dynamic and progressive process due to late radiation effects. Extra-cranial color-coded duplex sonography can be part of routine follow-up in NPC patients aged ≥50 years at 40 months post-radiotherapy.

Effects of external irradiation of the neck region on intima media thickness of the common carotid artery.

BACKGROUND: Several studies have shown that common carotid intima-media thickness (IMT) is increased after radiotherapy (RT) to the head and neck. However, further studies are needed to define the exact mechanism of radiation-induced injury in large vessels, investigate the relationship between radiation dose and large vessel injury and evaluate the rate of progress of atherosclerosis in irradiated vessels. OBJECTIVES: To investigate whether external irradiation to the carotid area has any effect on IMT of the common carotid artery in a group of patients who received RT vs control group matched for age, gender and race. METHODS: We studied 19 patients (10 male; 47.8 +/- 17.4 years) during a 5-month period (January 2009-July 2009); they had completed RT with a mean of 2.9 years before (range: 1 month-6 years) The mean radiation dose to the neck in the irradiated patients was 41.2 +/- 15.6 Gy (range: 25-70 Gy). Common carotid IMT was measured with echo-color Doppler. Nineteen healthy adult patients (10 male; 47.8 +/- 17.6) were recruited as a control group. RESULTS: IMT was not significantly higher in patients when compared to the control group (0.59 +/- 0.16 vs 0.56 +/- 0.16 mm, p = 0.4). There was no significant difference between the two groups in relation to the absence (p = 0.7) or presence (p = 0.6) of vascular risk factors. Although the difference did not reach statistical significance (p = 0.1), the irradiated young patients (age < or = 52 years) had IMT measurements higher (0.54 +/- 0.08 mm) than the non-irradiated young patients (0.49 +/- 0.14 mm). The mean carotid IMT increased with increasing doses of radiation to the neck (p = 0.04). CONCLUSION: This study shows that increased IMT of the common carotid artery after RT is radiation-dose-related. Therefore it is important to monitor IMT, which can be used as an imaging biomarker for early diagnosis of cerebrovascular disease in patients who have had radiotherapy for treatment of cancer of the head and neck and who are at increased risk for accelerated atherosclerosis in carotid arteries.

[Application of covered stent in the treatment of radiation-induced common carotid artery bleeding to a patient with nasoparyngeal carcinoma: a case report].

Bleeding is a rare but fatal complication after radiotherapy for nasoparyngeal carcinoma (NPC). In this article, we report an NPC case treated with radiotherapy complicated with bleeding of the common carotid artery(CCA). A 44-year-old man with NPC was treated with external radiotherapy 19 years ago, and a second course of treatment to the same field was administrated because of local nasoparyngeal recurrence 4 years ago. The patient was admitted to our hospital for massive bleeding. Conservative therapy including routine medication, blood transfusion and local compression showed almost no effect. Emergency carotid angiography revealed bleeding from the left CCA, and a self-expanding covered stent was deployed through percutaneous transluminal femoral approach. After the placement of the covered stent, angiography showed the bleeding was successfully controlled. So self-expanding covered stenting may be a safe, effective and minimal-invasive option for bleeding of the carotid artery. Long-term follow-up is required for further evaluation.

Radiation effects on the intima-media thickness of the common carotid artery in post-radiotherapy patients with head and neck malignancy.

BACKGROUND: Post-radiation large vessel injury has not received as much attention as microvascular irradiation injury. A few studies have shown that common carotid intima-media thickness (IMT) is increased after radiotherapy to the head and neck. However, in most of these studies, the irradiated subjects also had other major risk factors for atherosclerosis. In this study, irradiated subjects with major risk factors such as hypertension, diabetes, history of previous cerebrovascular accident and connective tissue disorder were excluded. OBJECTIVE: To show in a cross-sectional study if radiotherapy to the carotid area has any effect on the IMT of the common carotid artery. SUBJECTS AND METHODS: 13 patients with head and neck malignancies who had completed radiotherapy to the carotid region at least 1 year previously underwent ultrasound of the carotid artery. IMT measurements were compared with those of 13 healthy controls, matched for age, sex and race, with no history of radiotherapy. RESULTS: The irradiated subjects had significantly larger IMT measurements (mean 0.74 mm) than the non-irradiated subjects (mean 0.46 mm). The difference was significant (p<0.001) with a confidence interval of 95%. CONCLUSIONS: This study shows that there is a measurable, significant (p<0.001) increase in IMT of the common carotid artery after radiotherapy for head and neck malignancy compared with non-irradiated matched controls. This knowledge is important for risk-benefit assessment of prophylactic or therapeutic neck irradiation. Increased awareness of this complication should provide an opportunity to intervene and prevent future cerebrovascular accidents in the majority of such patients.

Increases in central retinal artery blood flow in humans following carotid artery and stellate ganglion irradiation with 0.6 to 1.6 microm irradiation.

The authors applied near-infrared low-level laser irradiation (LLLI) directed to the stellate ganglion (SG) and to the common carotid artery (CCA), and compared the effects on central retinal artery blood flow using color pulse Doppler sonography. In 10 healthy volunteers, LLLI (0.92 W, 1 : 1 duty cycle, 10 min) to both the SG and CCA significantly increased peak systolic blood velocity in the ophthalmic artery (p<0.001, each) and central retinal artery (p<0.001, each) without changes in vessel resistance. Irradiation to the CCA produced a stronger effect than that to the SG in the ophthalmic artery (p=0.007) and central retinal artery (p=0.031). These data suggest that LLLI to the SG or to the CCA is a useful therapy for increasing the retrobulbar blood flow, with irradiation directed to the CCA being more effective than that directed to the SG in clinical settings.

Accelerated progression of carotid stenosis in patients with previous external neck irradiation.

OBJECTIVE: Radiotherapy to the head and neck often results in carotid stenosis, but the course of disease is unknown. We investigated the natural history and progression of asymptomatic carotid stenosis induced by external irradiation. Patients and methods The study included 130 carotid arteries in 95 patients who had received external radiation therapy to the head and neck area and who had asymptomatic, mild internal carotid artery or common carotid artery stenosis. Stenosis of 15% to 49% on duplex ultrasound (US) scans defined mild (<50%) disease. Another 95 arteries in 74 patients with matched degree of carotid artery stenosis but who had not received radiation therapy were used as control. Both groups were followed up prospectively with serial duplex US scanning, and degree of carotid artery stenosis was categorized as 15% to 49%, 50% to 69%, 70% to 99%, and occlusion. Progression of carotid artery stenosis was defined as increase in stenosis from less than 50% to 50% or greater at ultrasonography. Secondary end points included progression to higher disease category, new cerebrovascular symptoms, and death. Data from irradiated arteries was compared with control data with the life table method. A Cox regression model was used to analyze disease progression, adjusted for covariates of sex, age, smoking, diabetes, and hypertension. RESULTS: Mean follow-up was 36 months. Adjusted freedom from progression rates at 3 years were 65% for irradiated arteries and 87% for control arteries at life-table analysis (P =.035; odds ratio, 3.1). The annualized progression rate from less than 50% to 50% or greater in irradiated arteries was 15.4%, compared with 4.8% in nonirradiated arteries. A long history of cervical irradiation (>6 years) was the only significant risk factor for disease progression. There was no difference between the two groups regarding development of new symptoms or mortality. CONCLUSIONS: Carotid stenosis associated with external irradiation progresses more rapidly compared with nonirradiated atherosclerotic arteries. Aggressive surveillance is recommended.

Beta radiation and inhibition of recanalization after coil embolization of canine arteries and experimental aneurysms: how should radiation be delivered?

BACKGROUND AND PURPOSE: Beta radiation prevents recanalization after coil embolization. We sought to determine the effects of varying coil caliber, length, activity of 32P per centimeter of coil or per volume, and spatial distribution of coils on recanalization. METHODS: We studied the angiographic evolution of 81 canine maxillary, cervical, and vertebral arteries implanted with a variety of nonradioactive (n=29 arteries) or radioactive (n=52) devices. We compared 1- or 2-caliber 0.015 or 0.010 coils ion-implanted or not with 3 different activity levels (0.05 to 0.08, 0.06 to 0.12, 0.18 to 0.32 microCi/cm) of 32P and totaling 4, 8, and 16 cm in length for the same arterial volume. We also compared inhibition of recanalization by beta radiation delivered by stents, after coil occlusion proximal to or within the stent, with that delivered by coils placed within nonradioactive stents. We finally studied the angiographic evolution of canine lateral wall carotid aneurysms treated with 1 or 2 stents of various activity levels positioned inside the parent artery across the neck. Animals were killed at 4 and 12 weeks for macroscopic photography and pathological examination. RESULTS: All arteries (29 of 29) occluded with nonradioactive devices were recanalized, while 49 of 52 arteries (94%) implanted with 32P devices were occluded at 4 weeks. All aneurysms treated with stents, radioactive or not, demonstrated residual filling of the sac or of channels leading to the aneurysms at follow-up angiography at 4 weeks. CONCLUSIONS: The recanalization process found in the canine arterial occlusion model is minimally affected by coil caliber, number, and length or packing density. Beta radiation reliably inhibits this process, but thrombosis is an essential condition for the efficacy of a radioactive coil strategy.

Could X-ray microbeams inhibit angioplasty-induced restenosis in the rat carotid artery?

BACKGROUND: Parallel, thin (<100 microm) planes of synchrotron-generated X rays, have been shown to spare normal tissues and preferentially damage tumors in animal models. The aim of the present study was to assess the effect of such microbeams directed unidirectionally on angioplasted rat carotid arteries. METHODS AND MATERIALS: Three groups of Sprague-Dawley rats were studied: (a) rats with normal, untreated arteries, (b) rats treated by balloon angioplasty, but not irradiated, and (c) rats treated with balloon angioplasty and exposed to single fraction, unidirectional, parallel, microbeams an hour after angioplasty. The microbeam array, 15 mm widex7.6 mm high, consisting of 27-microm-wide beam slices, spaced 200 microm center-to-center laterally traversed the damaged artery. The in-depth in-beam dose was 150 Gy, the "valley" dose (dose midway between microbeams resulting mainly from X-ray scattering) was 4.5 Gy on average, and the "integrated" (averaged) dose was 26 Gy. RESULTS: Microbeam irradiation, as given in the present study, was tolerated, but was insufficient to significantly suppress the neointimal hyperplasia. DISCUSSION: The microbeam dose used is considered low. Dose escalation would be necessary to reach conclusive results regarding the X-ray microbeam efficacy to control restenosis.

Topical application of beta-radiation to reduce intimal hyperplasia after carotid artery balloon injury in rabbit. A possible application for brachytherapy in vascular surgery.

PURPOSE: Endovascular brachytherapy for the prevention of intimal hyperplasia (IH) and restenosis after balloon/stent angioplasty has proven effective both in animal preparations and clinical trials. A variety of beta-emitting isotopes and catheter-based devices have been developed for the delivery of low-dose radiation in clinical coronary and peripheral trials. No platform, however, has yet been developed for brachytherapy in concert with vascular surgical operations. The purpose of this study was to evaluate the vascular histopathologic response following balloon injury to rabbit carotid arteries with and without topically applied low-dose beta-radiation. METHODS: The beta-emitting isotope strontium-90 (Sr-90) was conjugated onto the matrix of polypropylene (PLYP) mesh. Rabbit carotid arteries were balloon-injured with a #2 embolectomy catheter. Six carotid arteries were wrapped with nonradioactive PLYP mesh (controls) and Sr-90 ( approximately 90 microCi) PLYP mesh in order to deliver low-dose radiation to the vessel wall from the external (adventitial) surface. Tissue was harvested at 6 weeks and processed for histologic examination. RESULTS: There was consistent blockade of fibrocellular neointima formation with virtually no neointima present in all treated segments, compared to moderate neointima formation in controls. Medial thinning and smooth muscle cell (SMC) necrosis were also associated with topical brachytherapy. CONCLUSION: beta-Radiation applied by an externally wrapped PLYP mesh labeled with Sr-90 markedly suppressed neointima formation in an animal vascular surgical injury model. Further studies, however, are necessary to determine a suitable isotope and dosage for clinical application.