Detection of impending perfusion deficits by intraoperative computed tomography (iCT) in aneurysm surgery of the anterior circulation.

BACKGROUND: The aim of our study was to evaluate the additional benefit of intraoperative computed tomography (iCT), intraoperative computed tomography angiography (iCTA), and intraoperative computed tomography perfusion (iCTP) in the intraoperative detection of impending ischemia to established methods (indocyanine green videoangiography (ICGVA), microDoppler, intraoperative neuromonitoring (IONM)) for initiating timely therapeutic measures. METHODS: Patients with primary aneurysms of the anterior circulation between October 2016 and December 2019 were included. Data of iCT modalities compared to other techniques (ICGVA, microDoppler, IONM) was recorded with emphasis on resulting operative conclusions leading to inspection of clip position, repositioning, or immediate initiation of conservative treatment strategies. Additional variables analyzed included patient demographics, aneurysm-specific characteristics, and clinical outcome. RESULTS: Of 194 consecutive patients, 93 patients with 100 aneurysms received iCT imaging. While IONM and ICGVA were normal, an altered vessel patency in iCTA was detected in 5 (5.4%) and a mismatch in iCTP in 7 patients (7.5%). Repositioning was considered appropriate in 2 patients (2.2%), where immediate improvement in iCTP could be documented. In a further 5 cases (5.4%), intensified conservative therapy was immediately initiated treating the reduced CBP as clip repositioning was not considered causal. In terms of clinical outcome at last FU, mRS0 was achieved in 85 (91.4%) and mRS1-2 in 7 (7.5%) and remained mRS4 in one patient with SAH (1.1%). CONCLUSIONS: Especially iCTP can reveal signs of impending ischemia in selected cases and enable the surgeon to promptly initiate therapeutic measures such as clip repositioning or intraoperative onset of maximum conservative treatment, while established tools might fail to detect those intraoperative pathologic changes.

CT fluoroscopy-guided vertebral augmentation with a radiofrequency-induced, high-viscosity bone cement (StabiliT(®)): technical results and polymethylmethacrylate leakages in 25 patients.

OBJECTIVE: To assess the technical results of CT fluoroscopy-guided, radiofrequency-induced vertebral augmentation (StabiliT®) in terms of vertebral height restoration and polymethylmethacrylate (PMMA) leakages, occurring in 25 individual patients with vertebral compression fractures and osteolysis. MATERIALS AND METHODS: From 07/2010 to 08/2011, 25 patients (16 women, nine men; age 71 ± 14; range 41-89) with painful vertebral compression fractures due to osteoporosis (n = 19), metastases (n = 2) or multiple myeloma (n = 4) underwent vertebral augmentation with a radiofrequency-activated, high-viscosity polymethylmethacrylate (PMMA) bone cement (StabiliT® Vertebral Augmentation system; DFINE Europe GmbH, Mannheim) under local anesthesia. Thirty-four vertebrae (Th5-L5) were treated in 27 sessions under CT fluoroscopy guidance (128-row CT, Somatom Definition AS, Siemens, Erlangen) using a unilateral access and a cavity-creating osteotome prior to remote-controlled, hydraulically driven cement injection. 1/2/3 levels were treated in 21/5/1 session(s). Vertebral height change in the midsagittal plane (anterior, midvertebral, posterior endplate distance) and PMMA leaks were retrospectively evaluated using the postinterventional CT. RESULTS: All patients were successfully treated in the first session. Mean (MV ± SD) procedure time and amount of injected PMMA were 56 ± 14 min and 4.5 ± 1.4 ml, respectively. Mean anterior/midvertebral/posterior height gain was +7.1/+9.7/+0.4%. Small local vertebral leaks were observed in 18/34 vertebrae (53%) without any clinical sequelae. No major complications occurred. CONCLUSIONS: CT fluoroscopy-guided, RF-induced vertebral augmentation with a high-viscosity bone cement (StabiliT®) was safe and technically successful in all patients. Using a hydraulic cement injection technique, a moderate restoration of anterior and midvertebral height was seen while the system was not markedly superior to standard vertebroplasty regarding the frequency of minor asymptomatic PMMA leaks.

CT fluoroscopy-guided percutaneous vertebroplasty in spinal malignancy: technical results, PMMA leakages, and complications in 202 patients.

OBJECTIVE: To retrospectively evaluate the incidence and clinical impact of local polymethylmethacrylate (PMMA) leaks and pulmonary cement embolisms occurring under CT fluoroscopy-guided vertebroplasty of symptomatic malignant vertebral osteolyses. MATERIALS AND METHODS: From December 2001 to June 2009, 202 cancer patients (116 women, 86 men; age 63.2±8.6 years) with painful malignant vertebral osteolyses underwent vertebroplasty, with or without vertebral compression fracture. A total of 331 vertebrae were treated in 231 sessions under CT fluoroscopy guidance (120 kV; 10­25 mA; single slice, 4-, 16-, and 128-row CT). In the pre-vertebroplasty CT, the following items were assessed: osteolytic destruction (0, ≤25, ≤50, ≤75, or ≤100%) of vertebral cross-sectional area, posterior wall, and circumference; presence of perivertebral and degree of epidural (no, mild, moderate) soft tissue involvement. Local PMMA leaks were analyzed using the post-vertebroplasty CT. Pulmonary cement embolisms were evaluated in all patients having undergone radiography (CR; n053) or CT (n088) of the chest after vertebroplasty due to their underlying disease. Patient charts were reviewed regarding adverse events. RESULTS: Of 331 treated vertebrae, 32, 20.2, and 15.7% showed more than 50% osteolytic involvement of the vertebral cross-sectional area, posterior wall, and circumference, respectively. Mild or moderate epidural involvement was seen in 13.0 and 8.4%. Local PMMA leakage rate was 58.6% (194 of 331 vertebrae). Pulmonary cement embolisms (segmental, n010; central, n01) were seen after 7.8% of the procedures with follow-up imaging of the chest. No major complications occurred within a 30-day period after vertebroplasty. CONCLUSION: Vertebroplasty of spinal malignancy can be safely performed under CT fluoroscopy guidance even in patients with substantial osteolytic involvement. In our patient collective, PMMA leaks and pulmonary cement embolisms visualized in post-procedural radiography and CT images had no clinical impact.

Dual-room CT with a sliding gantry for intraoperative imaging: feasibility and workflow analysis of an interdisciplinary concept.

PURPOSE: Currently, intraoperative computed tomography (iCT) is a scarcely used technique in neurosurgery. It remains unclear whether this phenomenon is explained by unfavorable iCT-related workflows and/or a limited number of indications. We here analyzed workflows of an installed dual-room iCT (DR-iCT) as compared to surgical procedures lacking iCT. We compared infection rates, utilizations rates, and the spectrum of indications of DR-iCT with that of a previously used single-room iCT. METHODS: The study refers to a consecutive series of patients undergoing either single-room iCT (January 2014-August 2014) or DR-iCT (September 2014-July 2016). A further group undergoing surgery without iCT in the interconnected operating rooms represents the reference group. Workflow measurements and infection rates were calculated. Indications for iCT and utilization rates were compared for each of the devices. CT image quality was rated. RESULTS: Application of DR-iCT led to a broader use of this technique as compared to the single-room device, which concerned in particular stereotactic neurosurgery. Accordingly, iCT utilization rates significantly increased (up to 50.8 ± 4.6 surgeries per month, p < 0.001). Workflow was slightly prolonged in case of DR-iCT imaging; the difference, however, was not statistically significant. Infections rates were low (range 0.0-0.17 infections per month) and not influenced by the utilization rate. Image quality of the DR-iCT was classified as very good in 34/43 evaluated microsurgical patients. CONCLUSIONS: The use of DR-iCT enhances utilization rates with a broader field of indications for intraoperative imaging. Workflow measurements are not significantly prolonged. The technology is safe, and the imaging quality of modern devices can be expected to be good.

Stent-based approach for ventricle-to-coronary artery bypass.

BACKGROUND: Ventricle-to-coronary artery bypass (VCAB) is an experimental revascularization procedure that provides predominantly systolic instead of diastolic blood flow to a coronary artery. METHODS AND RESULTS: In a pig model, a stent-based procedure (VSTENT) was developed to create a VCAB. After thoracotomy, a covered VSTENT was implanted between the left ventricle and the left anterior descending coronary artery (LAD). Distal LAD flow, regional myocardial function, and intracoronary pressures were determined at different degrees of LAD stenosis and during complete LAD occlusion. During 3 hours of LAD occlusion, VSTENT preserved net forward flow at 70+/-6% and regional myocardial function at 71+/-8% of baseline. Preservation of net flow was influenced by the positioning of the VSTENT, with higher preservation also under conditions of increased oxygen demand if a "valve-like mechanism" was present during diastole. At a hemodynamically relevant level of LAD stenosis (>70%), systolic inflow was predominant after VSTENT implantation. Changes in mean diastolic intracoronary pressure that resulted from different degrees of LAD stenosis were linearly correlated to net flow after VSTENT implantation (r=0.88; P<0.001). CONCLUSIONS: VSTENT for ventricle-to-coronary artery bypass was feasible and preserved 70+/-6% of baseline flow during complete LAD occlusion. The degree of preservation was dependent on the position of the VSTENT creating a valve-like mechanism during diastole. Residual diastolic blood flow through a high-grade LAD stenosis influenced net flow favorably, because diastolic backflow decreased with increasing mean diastolic intracoronary pressure.

VEGF165 transfection decreases postischemic NF-kappa B-dependent myocardial reperfusion injury in vivo: role of eNOS phosphorylation.

Endothelial nitric oxide synthase (eNOS) phosphorylation increases nitric oxide formation, for example, after VEGF stimulation. We investigated whether nitric oxide formed after overexpression of VEGF or of phosphomimetic eNOS (S1177D) affects PMN-induced myocardial detriment after ischemia and reperfusion. Pigs (n=8 per group) were subjected to percutaneous liposome-based gene transfer by retroinfusion of the anterior interventricular vein 48 h before LAD occlusion (60 min) and reperfusion (24 h). Thereafter, regional myocardial function was assessed as subendocardial segment shortening (SES), and infarct size was determined. Tissue from the infarct region, the noninfarcted area at risk, and a control region was analyzed for NF-kappaB activation (EMSA), tumor necrosis factor (TNF)-alpha, and E-selectin mRNA and infiltration of polymorphonuclear neutrophils (PMN). L-NAME was applied in one group of VEGF-transfected animals. NF-kappaB activition, PMN infiltration in the infarct region, and AAR were reduced after transfection of VEGF or eNOS S1177D, but not after VEGF+L-NAME coapplication. Infarct size decreased, whereas SES improved after either VEGF or eNOS S1177D transfection, an effect inhibited by L-NAME coapplication. Retroinfusion of liposomal VEGF cDNA reduces NF-kappaB-dependent postischemic inflammation and subsequent myocardial reperfusion injury, an effect mediated at least in part by enhanced eNOS phosphorylation.

Feasibility of dynamic CT-based adenosine stress myocardial perfusion imaging to detect and differentiate ischemic and infarcted myocardium in an large experimental porcine animal model.

The purpose of the study is feasibility of dynamic CT perfusion imaging to detect and differentiate ischemic and infarcted myocardium in a large porcine model. 12 Country pigs completed either implantation of a 75 % luminal coronary stenosis in the left anterior descending coronary artery simulating ischemia or balloon-occlusion inducing infarction. Dynamic CT-perfusion imaging (100 kV, 300 mAs), fluorescent microspheres, and histopathology were performed in all models. CT based myocardial blood flow (MBFCT), blood volume (MBVCT) and transit constant (Ktrans), as well as microsphere's based myocardial blood flow (MBFMic) were derived for each myocardial segment. According to histopathology or microsphere measurements, 20 myocardial segments were classified as infarcted and 23 were ischemic (12 and 14 %, respectively). Across all perfusion states, MBFCT strongly predicted MBFMic (ß 0.88 ± 0.12, p < 0.0001). MBFCT, MBVCT, and Ktrans were significantly lower in ischemic/infarcted when compared to reference myocardium (all p < 0.01). Relative differences of all CT parameters between affected and non-affected myocardium were higher for infarcted when compared to ischemic segments under rest (48.4 vs. 22.6 % and 46.1 vs. 22.9 % for MBFCT, MBVCT, respectively). Under stress, MBFCT was significantly lower in infarcted than in ischemic myocardium (67.8 ± 26 vs. 88.2 ± 22 ml/100 ml/min, p = 0.002). In a large animal model, CT-derived parameters of myocardial perfusion may enable detection and differentiation of ischemic and infarcted myocardium.

High-resolution cine MRI with TGRAPPA for fast assessment of left ventricular function at 3 Tesla.

PURPOSE: To implement and evaluate the accuracy of multislice dual-breath hold cine MR for analysis of global systolic and diastolic left ventricular function at 3T. MATERIALS AND METHODS: 25 patients referred to cardiac MR underwent cine imaging at 3T (MAGNETOM Verio) using prospective triggered SSFP (TR 3.1 ms; TE 1.4 ms; FA 60°). Analysis of LV function was performed using a standard non-accelerated single-slice approach (STD) with multiple breath-holds and an accelerated multi-slice technique (TGRAPPA; R=4) encompassing the ventricles with 5 slices/breath-hold. Parameters of spatial and temporal resolution were kept identical (pixel: 1.9 × 2.5 mm(2); temporal resolution: 47 ms). Data of both acquisition techniques were analyzed by two readers using semiautomatic algorithms (syngoARGUS) with respect to EDV, ESV, EF, myocardial mass (MM), peak filling rate (PFR) and peak ejection rate (PER) including assessment of interobserver agreement. RESULTS: Volumetric results of the TGRAPPA approach did not show significant differences to the STD approach for left ventricular ejection fraction (62.3 ± 10.6 vs. 61.0 ± 8.4, P=0.2), end-diastolic volume (135.8 ± 47.5 vs. 130.8 ± 46.4, P=0.07), endsystolic volume (53.0 ± 29.7 vs. 53.1 ± 32.7, P=0.99) and myocardial mass (114.2 ± 32.5 vs. 114.6±30.6, P=0.9). Moreover, a comparison of peak ejection rate (601.3 ± 190.2 vs. 590.8 ± 218.2, P=0.8) and peak filling rate (535.1±191.2 vs. 535.4 ± 210.7, P=0.99) did not reveal significant differences between the two groups. Limits in interobserver agreement were low for all systolic and diastolic parameters in both groups (P ≥ 0.05). Total acquisition time for STD was 273 ± 124 s and 34 ± 5 s for TGRAPPA (P ≤ 0.001). Evaluation time for standard and multislice approach was equal (10.8 ± 1.4 vs. 9.8 ± 2.1 min; P=0.08).

Myocardial CT perfusion imaging in a large animal model: comparison of dynamic versus single-phase acquisitions.

OBJECTIVES: This study sought to compare dynamic versus single-phase high-pitch computed tomography (CT) acquisitions for the assessment of myocardial perfusion in a porcine model with adjustable degrees of coronary stenosis. BACKGROUND: The incremental value of the 2 different approaches to CT-based myocardial perfusion imaging remains unclear. METHODS: Country pigs received stent implantation in the left anterior descending coronary artery, in which an adjustable narrowing (50% and 75% stenoses) was created using a balloon catheter. All animals underwent CT-based rest and adenosine-stress myocardial perfusion imaging using dynamic and single-phase high-pitch acquisitions at both degrees of stenosis. Fluorescent microspheres served as a reference standard for myocardial blood flow. Segmental CT-based myocardial blood flow (MBFCT) was derived from dynamic acquisitions. Segmental single-phase enhancement (SPE) was recorded from high-pitch, single-phase examinations. MBFCT and SPE were compared between post-stenotic and reference segments, and receiver-operating characteristic curve analysis was performed. RESULTS: Among 6 animals (28 ± 2 kg), there were significant differences of MBFCT and SPE between post-stenotic and reference segments for all acquisitions at 75% stenosis. By contrast, although for 50% stenosis at rest, MBFCT was lower in post-stenotic than in reference segments (0.65 ± 0.10 ml/g/min vs. 0.75 ± 0.16 ml/g/min, p < 0.05), there was no difference for SPE (128 ± 27 Hounsfield units vs. 137 ± 35 Hounsfield units, p = 0.17), which also did not significantly change under adenosine stress. In receiver-operating characteristic curve analyses, segmental MBFCT showed significantly better performance for ischemia prediction at 75% stenosis and stress (area under the curve: 0.99 vs. 0.89, p < 0.05) as well as for 50% stenosis, regardless of adenosine administration (area under the curve: 0.74 vs. 0.57 and 0.88 vs. 0.61, respectively, both p < 0.05). CONCLUSIONS: At higher degrees of coronary stenosis, both MBFCT and SPE permit an accurate prediction of segmental myocardial hypoperfusion. However, accuracy of MBFCT is higher than that of SPE at 50% stenosis and can be increased by adenosine stress at both degrees of stenosis.

Accuracy of dynamic computed tomography adenosine stress myocardial perfusion imaging in estimating myocardial blood flow at various degrees of coronary artery stenosis using a porcine animal model.

OBJECTIVE: To determine the accuracy of computed tomography (CT) dynamic stress myocardial perfusion imaging to estimate myocardial blood flow (MBF) in a porcine animal model with variable degrees of induced coronary artery stenosis in comparison with microsphere-derived MBF. METHODS AND MATERIALS: Seven domestic pigs (36 ± 4 kg) received stents (confirmed 3.0 mm diameter) in the left anterior descending coronary artery distal to first diagonal branch. A balloon catheter was placed within the stent and inflated to various degrees to obtain a defined luminal narrowing (50% and 75% diameter stenosis) as confirmed by intra-arterial flow wire measurement. All models underwent adenosine-mediated (140 µg/kg/min) dynamic stress and rest myocardial perfusion CT imaging using a dual-source CT scanner (shuttle-mode with 100 kV/300 mAs, 20 mL iopromide) with prospective acquisitions every second heartbeat for 30 seconds. CT-estimated MBF (MBFCT) was calculated using a model-based parametric deconvolution method and correlated to that of fluorescent microspheres (MBFmic) injected at each perfusion state. RESULTS: All study procedures were performed without complications, and all animals completed the study protocol. Among 448 myocardial segments, 31 (7%) were considered nonevaluable because of motion artifacts. With stress, MBFCT increased significantly (1.10 ± 0.25 vs. 0.80 ± 0.28 mL/g/min, P < 0.001; at stress and rest, respectively) in all myocardial segments and correlated with MBFmic (r = 0.67, P < 0.001). MBFCT overestimated MBFmic, independently of adenosine-stress and degree of coronary stenosis (ß = 2.3, 95% confidence interval: 1.81-2.79 mL/g/min, P < 0.001). Although there were no differences in MBFCT between 50% and 75% coronary stenosis at rest (0.01 ± 0.08 mL/g/min, P = 0.86), MBFCT was significantly lower at 75% than at 50% under stress conditions (0.53 ± 0.19 vs. 0.71 ± 0.24 mL/g/min, P = 0.002). CONCLUSIONS: CT-derived MBF measurements at rest and stress with varying degrees of coronary stenosis show a valid difference but an underestimated correlation with microsphere-derived MBF in a porcine animal model.

Unsupervised fully automated inline analysis of global left ventricular function in CINE MR imaging.

OBJECTIVES: To implement and evaluate the accuracy of unsupervised fully automated inline analysis of global ventricular function and myocardial mass (MM). To compare automated with manual segmentation in patients with cardiac disorders. MATERIALS AND METHODS: In 50 patients, cine imaging of the left ventricle was performed with an accelerated retrogated steady state free precession sequence (GRAPPA; R = 2) on a 1.5 Tesla whole body scanner (MAGNETOM Avanto, Siemens Healthcare, Germany). A spatial resolution of 1.4 x 1.9 mm was achieved with a slice thickness of 8 mm and a temporal resolution of 42 milliseconds. Ventricular coverage was based on 9 to 12 short axis slices extending from the annulus of the mitral valve to the apex with 2 mm gaps. Fully automated segmentation and contouring was performed instantaneously after image acquisition. In addition to automated processing, cine data sets were also manually segmented using a semi-automated postprocessing software. Results of both methods were compared with regard to end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and MM. A subgroup analysis was performed in patients with normal (> or =55%) and reduced EF (<55%) based on the results of the manual analysis. RESULTS: Thirty-two percent of patients had a reduced left ventricular EF of <55%. Volumetric results of the automated inline analysis for EDV (r = 0.96), ESV (r = 0.95), EF (r = 0.89), and MM (r = 0.96) showed high correlation with the results of manual segmentation (all P < 0.001). Head-to-head comparison did not show significant differences between automated and manual evaluation for EDV (153.6 +/- 52.7 mL vs. 149.1 +/- 48.3 mL; P = 0.05), ESV (61.6 +/- 31.0 mL vs. 64.1 +/- 31.7 mL; P = 0.08), and EF (58.0 +/- 11.6% vs. 58.6 +/- 11.6%; P = 0.5). However, differences were significant for MM (150.0 +/- 61.3 g vs. 142.4 +/- 59.0 g; P < 0.01). The standard error was 15.6 (EDV), 9.7 (ESV), 5.0 (EF), and 17.1 (mass). The mean time for manual analysis was 15 minutes. CONCLUSIONS: Unsupervised fully automated segmentation and contouring during image reconstruction enables an accurate evaluation of global systolic cardiac function.

Left ventricular volumes and mass in marathon runners and their association with cardiovascular risk factors.

BACKGROUND: To assess left ventricular volumes and mass by cardiac magnetic resonance imaging in relation to conventional cardiovascular risk factors and coronary atherosclerotic plaque burden in master marathon runners aged > or =50 years. METHODS: Cardiac MRI was performed in 105 clinically healthy male marathon runners (mean age 57.3 +/- 5.7 years, range 50-71 years) on a 1.5 T MR system (Avanto, Siemens, Germany). Cine steady state free precession images in standard long and short axes views were acquired to assess left ventricular volumes and mass. Cardiovascular risk factors (blood pressure, HDL/LDL cholesterol, smoking, body mass index) were assessed and coronary artery calcification (CAC) was quantified by electron beam computed tomography. RESULTS: Left ventricular muscle mass (mean LVMM = 140 +/- 27 g; 73 +/- 13 g/m(2)) increased with increasing left ventricular end-diastolic volume (mean LVEDV = 137 +/- 32 ml; 72 +/- 15 ml/m(2)) (r = 0.41, P < 0.0001) and with systolic (r = 0.33, P = 0.005) and diastolic (r = 0.28, P = 0.005) blood pressures. Left ventricular EDV increased up to the age of 55 years, but decreased thereafter. Runners with LVMM > or =150 g had significantly higher CAC scores than runners with LVMM <150 g (median CAC score 110 vs. 25, P = 0.04). CONCLUSIONS: Increases in LVMM and LVEDV may not only represent a response to exercise but are dependent on age and blood pressure, also. In addition, a left ventricular hypertrophy without an increase in volume may be an indicator for early subclinical cardiac alterations in response to risk factor exposure.

Accuracy of accelerated cine MR imaging at 3 Tesla in longitudinal follow-up of cardiac function.

The ability of fast, parallel-imaging-based cine magnetic resonance (MR) to monitor global cardiac function in longitudinal exams at 3 Tesla was evaluated. Seventeen patients with chronic cardiac disease underwent serial cine MR imaging exams (n=3) at 3 Tesla. Data were acquired in short-axis orientation using cine steady-state free precession (SSFP) with a spatial resolution of 2.5 x 1.9 mm(2) at 45 ms temporal resolution. Multislice imaging (three slices/breath-hold) was performed using TSENSE acceleration (R=3) and standard single-slice cine (non-TSENSE) was performed at identical locations in consecutive breath-holds. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and myocardial mass (MM) of both cine approaches were compared for individual time-points as well as for longitudinal comparison. TSENSE-cine did not show significant differences for EDV (2.6 ml; P=0.79), ESV (2.2 ml; P=0.81), EF (-0.3%; P=0.95) and MM (2.4 g; P=0.72) in comparison with non-TSENSE. Longitudinal ANOVA analysis did not reveal significant differences for any parameter, neither for non-TSENSE data (all P>0.7) nor for TSENSE data (all P>0.9). Multifactorial ANOVA showed non-significant differences (all P>0.7) at comparable data variances. Data acquisition was significantly shortened using TSENSE. Threefold accelerated multislice cine at 3 Tesla allows accurate assessment of volumetric LV data and accurate longitudinal monitoring of global LV function at a substantially shorter overall examination time.

Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins: comparison with surgical and percutaneous intramyocardial gene delivery.

OBJECTIVES: We sought to study adenoviral gene delivery using percutaneous selective pressure-regulated retroinfusion and to compare it directly with surgical and percutaneous intramyocardial delivery (PIMD) for the first time. BACKGROUND: Intramyocardial delivery (IMD) has been recommended to be the preferred gene delivery strategy so far. However, surgical and percutaneous intramyocardial injection lead to incomplete retention of the injected viral vectors and to limited spatial myocardial distribution. Percutaneous selective pressure-regulated retroinfusion of the coronary veins was developed recently to provide an effective and more homogenous regional myocardial gene transfer. METHODS: In 15 pigs, adenoviral vectors (Ad2-CMV beta-galactosidase [beta-gal] 5 x 10(9) pfu) were applied via surgical IMD (n = 5), PIMD (n = 5), and selective pressure-regulated retroinfusion (n = 5). Seven days after gene transfer, myocardial beta-gal expression was measured by ELISA. RESULTS: Selective retroinfusion into the anterior cardiac vein substantially increased reporter gene expression (1,039 +/- 79 pg beta-gal/mg protein) in the targeted left anterior descending coronary artery territory when compared with surgical (448 +/- 127, p < 0.05) and PIMD (842 +/- 145, p < 0.05). Both IMD approaches showed an inhomogenous beta-gal expression, particularly along the injection sites, while retroinfusion resulted in a more homogenous transmural gene expression. CONCLUSIONS: Percutaneous selective pressure-regulated retroinfusion compares favorably with surgical and percutaneous intramyocardial injection techniques by providing a more homogenous and even more efficient adenoviral gene delivery.