High-frequency Power Doppler Research Articles

Ultrasound-stimulated microbubbles enhancement of fractionated radiation for tumor treatment.

Radiation therapy (XRT) causes numerous biological changes in tumor microenvironment. Radiation vascular response, due to endothelial disruption, can influence treatment outcomes in a dose-dependent manner. Ultrasound-stimulated microbubbles (USMB) have also been demonstrated to create a vascular response in the tumor microenvironment and enhance tumor response when used in combination with XRT. Single doses of 8-10Gy are known to induce activation of acid sphingomyelinase (ASMase)-induced ceramide production, causing vascular damage. Destruction of vasculature results in endothelial apoptosis followed by tumor cell death. The effect of tumor response is known to be synergistic by 10-fold higher cell kill observed when USMB is combined with radiation. In this study, we used an USMB approach in combination with conventional low dose fractionated radiation to enhance endothelial cell responses to XRT in human PC3 prostate cancer xenograft model. Mice were divided into untreated, USMB therapy, fractionated XRT, and combined USMB therapy followed by XRT (USMB + XRT) groups. USMB therapy was delivered twice per week in the USMB-alone and combined USMB + XRT treatment groups over four weeks. Radiation treatments were delivered in fractions of 2Gy/day (total 40Gy in 20 fractions, BED10 = 48Gy) in the XRT-alone and combined USMB + XRT groups. The treatment outcome was evaluated using histopathology, power Doppler, and immunohistochemistry assays. Tumor growth assessment showed that sizes of tumors increased in the control and the single treatment groups over a treatment period of four weeks, but significantly decreased with the combined treatments of USMB + XRT. Immunohistochemical analysis indicated a statistically significant vascular disruption in mice that received treatment involving a full 4-week schedule of combined (USMB + XRT) treatments. A statistically significant increase in vascular disruption was demonstrated through CD68 and trichrome fibrosis staining. Changes in local perfusion assessed using high-frequency power Doppler imaging demonstrated attenuated blood flow in the combined group. This work demonstrates the efficacy of using USMB as a radiation sensitizer in a mouse model of human PC3 tumor xenograft. This radiation treatment enhancement modality has the advantage of targeting tumor vasculature with ultrasound stimulation that can be implemented prior to radiation treatment.

The Use of Doppler Ultrasound to Assess the Blood Flow of Pedicled Vascularized Bone Grafting for Scaphoid Nonunions.

Objectives This study aims to assess the blood flow and the vascularity pattern across the newly bridged vascularized bone grafts for scaphoid nonunions using three-dimensional (3D) high frequency power Doppler ultrasonography and its role in the union. Materials and Methods A total of 26 patients with scaphoid nonunions were operated with 1,2-intercompartmental supraretinacular artery (ICSRA) graft. CT scan and 3D high frequency power Doppler ultrasonography were performed in all patients between 12 and 18 weeks, and its results were analyzed. Results Doppler ultrasonography confirmed the pulsatile flow and vascularity across the pedicle and vascularized bone graft incorporation into the scaphoid nonunion site. Conclusions 3D high frequency power Doppler ultrasonography is a simple, noninvasive, nonradiation, reproducible, and well-reliable diagnostic modality in assessing the blood flow and vascularity of the bone grafts used for scaphoid nonunions. Level of Evidence This is a Level IV study.

Non‐invasive three‐dimensional power Doppler imaging for the assessment of acute cerebral blood flow alteration in a mouse model of subarachnoid haemorrhage

We aimed to evaluate the feasibility of a non-invasive method of cerebral blood flow (CBF) measurement using high-frequency power Doppler ultrasound imaging in a mouse model of subarachnoid haemorrhage (SAH). The 3-dimensionally (3D) reconstructed blood flow signals (%vascularity) within the brain volume of the middle cerebral artery territory correlated well with reference parameters, baseline carotid artery blood flow (r2 =0.52, P<0.0001) and normalized CBF changes (r2 =0.74 P<0.0001). These data suggest that the 3D power Doppler analysis may have the potential for reflecting real-time CBF changes during the acute phase of experimental SAH, which may be applicable to preclinical studies on early brain injury.

High-frequency power Doppler ultrasonography in the assessment of nail psoriasis

High-frequency power Doppler ultrasonography in the assessment of nail psoriasis

High frequency power doppler ultrasonography in oligoarticular juvenile idiopathic arthritis: Correlation with disease severity

Aim of the workJuvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is a leading cause of acquired disability in the pediatric age. We aimed to detect subclinical synovitis in children with oligoarticular JIA using high frequency power Doppler ultrasonography (US) and correlate US scores with clinical disease severity. Patients and methodsHigh frequency power Doppler ultrasonography was done for both knees and ankles of 20 oligoarticular JIA patients. Assessment of clinical disease severity by articular index scores and functional assessment by the modified juvenile arthritis functionality scale (JAFS) were calculated for all patients. ResultsWe found 24 clinically active knees and 20 clinically active ankles. On comparison between clinical and ultrasonography activity, we found 13 clinically inactive joints, but they were active joints by ultrasonography. There was a highly significant difference (p<0.001) between clinical and US activity as regards the number of affected joints. There was a highly significant (p<0.01) positive correlation between clinical disease severity scores and all US scores except clinical score of range of motion (ROM); that did not show a significant positive correlation with US score of effusion (p>0.05). ConclusionsHigh frequency power Doppler US may be useful in detecting subclinical synovitis of joints in JIA patients with clinically defined inactive joints. Also, it can indicate the degree of disease severity in JIA patients. So, high frequency power Doppler US can be used in standard clinical practice for monitoring JIA patients for better assessment and management of the disease.

A Method to Validate Quantitative High-Frequency Power Doppler Ultrasound With Fluorescence in Vivo Video Microscopy

Flow quantification with high-frequency (>20 MHz) power Doppler ultrasound can be performed objectively using the wall-filter selection curve (WFSC) method to select the cutoff velocity that yields a best-estimate color pixel density (CPD). An in vivo video microscopy system (IVVM) is combined with high-frequency power Doppler ultrasound to provide a method for validation of CPD measurements based on WFSCs in mouse testicular vessels. The ultrasound and IVVM systems are instrumented so that the mouse remains on the same imaging platform when switching between the two modalities. In vivo video microscopy provides gold-standard measurements of vascular diameter to validate power Doppler CPD estimates. Measurements in four image planes from three mice exhibit wide variation in the optimal cutoff velocity and indicate that a predetermined cutoff velocity setting can introduce significant errors in studies intended to quantify vascularity. Consistent with previously published flow-phantom data, in vivo WFSCs exhibited three characteristic regions and detectable plateaus. Selection of a cutoff velocity at the right end of the plateau yielded a CPD close to the gold-standard vascular volume fraction estimated using IVVM. An investigator can implement the WFSC method to help adapt cutoff velocity to current blood flow conditions and thereby improve the accuracy of power Doppler for quantitative microvascular imaging.

Abstract 131: Mitogen-Activated Protein Kinase Kinase Activation is Necessary for Macrophage Accumulation, Compensatory Growth of Blood Vessels and Muscle Regeneration Following Femoral Artery Ligation

Lower limb peripheral vascular disease (PVD) results from the occlusion of arteries leading to reduced blood flow and limb ischemia. Compensatory growth of blood vessels may be sufficient to overcome limb ischemia but for some patients therapeutic intervention, even limb amputation, is required. To gain insight into the mechanisms regulating compensatory growth of blood vessels we used a mouse model of hindlimb ischemia. The ischemic lesions were confirmed and compensatory arteriogenesis was evaluated by high frequency power Doppler ultrasound. In this model, compensatory growth occurs mainly through arteriogenesis. While signaling by mitogen activated protein kinase kinases 1 and 2 (MEK 1 and 2) is required for developmental and tumor angiogenesis, it is unknown whether MEK1/2 activity drives other physiologic vascular growth such as arteriogenesis. We hypothesized that MEK 1/2 activity is necessary for hindlimb re-vascularization following femoral artery ligation. To test this we ligated the femoral artery in mice and then treated them with PD0325901, an allosteric MEK1/2 inhibitor. Following femoral artery ligation active MEK signaling was detected in spindle-shaped cells located within regions of intense angiogenesis and myocyte proliferation. MEK inhibition with PD0325901 reversibly blocked neovascularization, muscle regeneration, and caused extensive coagulative necropathy. MEK inhibition not only prevented arteriogenesis in ischemic limbs but also caused a reduction in arterial diameter. Finally, MEK inhibition prevented accumulation of CD68+ cells in ischemic tissues and skewed systemic cytokine expression towards a persistent, pro-inflammatory phenotype. Our investigation provides pharmacologic evidence demonstrating an essential role for MEK signaling in angiogenesis and arteriogenesis in response to hind limb ischemia. Further, we observed activation of MEK signaling is required for accumulation of macrophages in ischemic tissues and prevents down-regulation of systemic pro-inflammatory cytokines. Lastly, since the effects of MEK inhibition on reperfusion are reversible, we can use MEK inhibitors to create a mouse model of chronic limb ischemia that mimics aspects of PVD.

Ultrasound-Mediated Microbubble Enhancement of Radiation Therapy Studied Using Three-Dimensional High-Frequency Power Doppler Ultrasound

Tumor responses to high-dose (>8 Gy) radiation therapy are tightly connected to endothelial cell death. In the study described here, we investigated whether ultrasound-activated microbubbles can locally enhance tumor response to radiation treatments of 2 and 8 Gy by mechanically perturbing the endothelial lining of tumors. We evaluated vascular changes resulting from combined microbubble and radiation treatments using high-frequency 3-D power Doppler ultrasound in a breast cancer xenograft model. We compared treatment effects and monitored vasculature damage 3 hours, 24 hours and 7 days after treatment delivery. Mice treated with 2 Gy radiation and ultrasound-activated microbubbles exhibited a decrease in vascular index to 48 ± 10% at 24 hours, whereas vascular indices of mice treated with 2 Gy radiation alone or microbubbles alone were relatively unchanged at 95 ± 14% and 78 ± 14%, respectively. These results suggest that ultrasound-activated microbubbles enhance the effects of 2 Gy radiation through a synergistic mechanism, resulting in alterations of tumor blood flow. This novel therapy may potentiate lower radiation doses to preferentially target endothelial cells, thus reducing effects on neighboring normal tissue and increasing the efficacy of cancer treatments.

A method to validate quantitative high-frequency power Doppler ultrasound with fluorescence in vivo video microscopy

Flow quantification with high-frequency power Doppler ultrasound can be performed using the wall-filter selection curve (WFSC) method [Elfarnawany et al., Ultrasound Med. Biol. 38, 1429–1439 (2012)]. The WFSC method plots color pixel density (CPD) as a function of wall filter cut-off velocity as a means of objectively selecting an operating point cut-off velocity. In this study, an in vivo video microscopy (IVVM) system was used to measure the size of small (140–400 μm diameter) mouse testicular vessels immediately after the vessels were imaged with 30 MHz power Doppler. The mouse remained on the same platform throughout ultrasound and IVVM imaging. Measurements in four image planes from three mice demonstrated that, similar to previously reported flow-phantom data, in vivo WFSCs exhibit distinct, sloped “characteristic intervals” at cut-off velocities where the CPD approaches the gold-standard IVVM estimate of vascular volume fraction. A wide range of operating point cut-off velocities (4.5 to 12 mm/s) was obtained, which indicates that use of a predetermined cut-off can produce substantial errors in cross-sectional studies that employ power Doppler to quantify vascularity. The WFSC method is a promising strategy for adapting the cut-off velocity to intersubject and longitudinal variations in blood flow during microvascular imaging experiments.

Dose-dependent response of tumor vasculature to radiation therapy in combination with Sunitinib depicted by three-dimensional high-frequency power Doppler ultrasound

Large doses of radiation (8-20 Gy) preferentially target tumor vasculature. This vascular response is suggested to regulate tumor response to radiotherapy. Here, we investigate the relative contributions of direct cell killing by radiation versus tumor cell death due to radiation effects on the vasculature. We also examine Sunitinib's mechanism of action as a tumor radiosensitizer. MDA-MB-231 xenografts were treated with radiation doses of 2-16 Gy alone, or in combination with bFGF (endothelial radio-protector) or Sunitinib as pharmacological modulators of the vasculature. Sunitinib was orally administered for 2 weeks at 30 mg/kg before radiotherapy; bFGF was intravenously injected 1 h prior to irradiation. Three-dimensional high-frequency power Doppler ultrasound was used to assess relative changes in tumor vasculature. Immunohistochemistry, clonogenic and tumor growth assays were used to quantify tumor response. Significant reductions in power Doppler signal of up to 50 % were observed for 8 and 16 Gy treatments, along with a dose-dependent increase in cell death. No significant change in power Doppler signal and minimal tumor cell death were noted for tumors treated with radiation and bFGF. Treatments where Sunitinib was combined with radiation demonstrated a significant increase in flow signal at doses equal or greater than 8 Gy. This was accompanied with a significant increase in cell death when compared to radiation or Sunitinib alone. We confirm that tumor response to high doses of radiation is regulated by its vasculature. We also posit that the response observed when radiation is combined with Sunitinib is linked to a vascular "normalization" effect.

Stimulated Angiogenesis for Fracture Healing Augmented by Low-Magnitude, High-Frequency Vibration in A Rat Model—Evaluation of Pulsed-Wave Doppler, 3-D Power Doppler Ultrasonography and Micro-CT Microangiography

This study aimed to investigate the mechanism of low-magnitude high-frequency vibration (LMHFV) treatment on angiogenesis and blood flow for enhancement of fracture healing. Nine-month-old ovariectomized (OVX) and sham-operated (Sham) rats received closed fractures creation at the femora and were randomized into LMHFV treatment (Sham-V, OVX-V) or control (Sham-C, OVX-C) groups. Pulsed-wave Doppler indicated an increase in blood flow velocity of the femoral artery at weeks 2 (OVX pair: p = 0.030) and 4 (OVX pair: p = 0.012; Sham pair: p = 0.020) post-treatment. Significantly enhanced vascular volume (VV) at the fracture site in the vibration groups was demonstrated by 3-D high-frequency power Doppler at week 2 (Sham pair: p = 0.021) and micro–computed tomography (microCT) microangiography at weeks 2 (OVX pair: p = 0.009) and 4 (OVX pair: p = 0.034), which echoed the osteogenesis findings by radiographic and microCT analysis. VV in the OVX groups was inferior to the Sham groups. However, OVX-V showed higher percentages of angiogenic enhancement than Sham-V. Despite impaired neo-angiogenesis in osteoporotic fractures, LMHFV could increase blood flow and angiogenesis in both normal and osteoporotic fractures, thus enhancing fracture healing.

Three‐dimensional high frequency power Doppler ultrasonography for the assessment of microvasculature during fracture healing in a rat model

We aimed to establish a novel approach with 3D high frequency power Doppler ultrasonography (3D-HF-PDU) to assess microvasculature at the fracture site in rat femurs by comparing with microCT-based microangiography. Twenty-four 9-month-old ovariectomized (OVX) osteoporotic rats and age-matched sham-ovariectomized (Sham) rats were used for establishing closed fracture models on right femora. At 2, 4, and 8 weeks post-operatively, four rats in each group underwent in vivo 3D-HF-PDU scanning for evaluation of vascularization and blood flow at the fracture site. Then the fractured femora were harvested for ex vivo microangiography, and neovasculatures within the callus were reconstructed for vascular volume analysis. Correlation between the vascular volumes of the two methodologies was examined. Both 3D-HF-PDU and microangiography showed a decline of vascular volume at the fracture site from 2 to 8 weeks and a significantly larger volume in the Sham group than the OVX group. A significant linear positive correlation (r = 0.87, p < 0.001) was detected between the volumes measured by the two methodologies. Osteoporotic rats had a diminished angiogenic response and lower blood perfusion than Shams. We believe 3D-HF-PDU is feasible and reproducible for in vivo assessment of microvasculature during femoral fracture healing in rats.

Investigating the effects of intensity threshold on high-frequency three-dimensional power Doppler ultrasound.

High-frequency power Doppler ultrasound is a non-invasive vascular imaging modality ideal for a quantitative assessment of vascularity in preclinical models. Although it permits detecting slower blood flows than other ultrasound Doppler methods, it is limited by flow artifacts, complicating the interpretation of tumor vascularity metrics such as the vascularity index (VI). Our aim was to examine how parameters such as the intensity threshold affect the VI in in vivo xenograft models. Breast MDA-MB-231 tumors in the hind leg of SCID mice were treated with 0 or 8 Gy radiation, and imaged before and 24 h after treatment. A Vevo770 was used along with a 25-MHz center frequency transducer to obtain 3-D power Doppler images of tumors. Mice were again imaged while in the same position 1 min after sacrifice at 24 h. This was carried out for direct comparison of true blood flow signal to system noise level. The VI was computed for a range of intensity thresholds. The VI-threshold curves varied differently as a function of treatment, and preliminary data indicate an optimal plateau where the intensity threshold should be set, yielding a nearly true blood flow signal and minimizing noise signal. [Work funded by the Canadian Breast Cancer Foundation.]

The wall-filter selection curve method for objective tuning of power Doppler clutter filter cutoff velocity.

High-frequency power Doppler ultrasound is commonly used to assess vascularity in small-animal cancer models, but quantitative images can be difficult to obtain in the presence of clutter artifacts. To improve vascular quantification, the color pixel density (CPD) in a region of interest can be plotted as a function of wall-filter cutoff velocity to produce the wall-filter selection curve. A mathematical model based on receiver operating characteristic statistics was developed to guide the interpretation of wall-filter selection curves. Mathematical predictions were tested using a VisualSonics Vevo 770 system with a 30-MHz transducer and a flow phantom containing four 200–300-μm-diameter vessels. The phantom mimicked vessel configurations observed in micro-CT images of a transgenic mouse prostate cancer model. Selection curves characteristically include a plateau whose CPD may correspond to either the total vascular volume fraction or to the volume fraction of a subset of vessels in the region. The flow-phantom data indicate that the plateau provides a reliable estimate of total vascularity if the plateau begins at a cutoff velocity &amp;lt;2 mm/s and is longer than 0.5 mm/s. The wall-filter selection curve may enable adaptation of scanner settings to changing flow conditions as a tumor progresses during a longitudinal study.

Objective Selection of High-Frequency Power Doppler Wall Filter Cutoff Velocity for Regions of Interest Containing Multiple Small Vessels

High-frequency (> 20 MHz) power Doppler ultrasound is frequently used to quantify vascularity in preclinical studies of small animal angiogenic models, but quantitative images can be difficult to obtain in the presence of flow artifacts. To improve flow quantification, color pixel density (CPD) can be plotted as a function of wall filter cutoff velocity to produce a wall-filter selection curve that can be used to estimate actual vascular volume fraction. A mathematical model based on receiver operating characteristic statistics is developed to study the behavior of wall-filter selection curves. The model is compared to experimental data acquired with a 30-MHz transducer and a custom-designed multiple-vessel flow phantom capable of mimicking a range of blood vessel sizes (200-300 microm), blood flow velocities (1-10 mm/s), and blood vessel orientations. At high flow rates, wall-filter selection curves for multiple-vessel regions include a plateau whose CPD corresponds with the total vascular volume fraction. Conversely, the vascular volume fraction of a subset of vessels is obtained at low flow rates. Detection of the volume fraction of all vessels is ensured when a plateau is > 0.5 mm/s in length and begins at a wall filter cutoff < 2 mm/s.

Photoacoustic and high-frequency power Doppler ultrasound biomicroscopy: a comparative study

Both photoacoustic imaging and power Doppler ultrasound are capable of producing images of the vasculature of living subjects, however, the contrast mechanisms of the two modalities are very different. We present a quantitative and objective comparison of the two methods using phantom data, highlighting relative merits and shortcomings. An imaging system for combined photoacoustic and high-frequency power Doppler ultrasound microscopy is presented. This system uses a swept-scan 25-MHz ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so that photoacoustic and power Doppler ultrasound images can be coregistered. Experiments are performed on flow phantoms with various combinations of vessel size, flow velocity, and optical wavelength. For the task of blood volume detection, power Doppler is seen to be advantageous for large vessels and high flow speeds. For small vessels with low flow speeds, photoacoustic imaging is seen to be more effective than power Doppler at the detection of blood as quantified by receiver operating characteristic analysis. A combination of the two modes could provide improved estimates of fractional blood volume in comparison with either mode used alone.

Detectability of Small Blood Vessels with High-Frequency Power Doppler and Selection of Wall Filter Cut-Off Velocity for Microvascular Imaging

Power Doppler imaging of physiologic and pathologic angiogenesis is widely used in preclinical studies to track normal development, disease progression and treatment efficacy but can be challenging given the presence of small blood vessels and slow flow velocities. Power Doppler images can be plagued with false-positive color pixels or undetected vessels, thereby complicating the interpretation of vascularity metrics such as color pixel density (CPD). As an initial step toward improved microvascular quantification, flow-phantom experiments were performed to establish relationships between vessel detection and various combinations of vessel size (160, 200, 250, 300 and 360 μm), flow velocity (4, 3, 2, 1 and 0.5 mm/s) and transducer frequency (30 and 40 MHz) while varying the wall filter cut-off velocity. Receiver operating characteristic (ROC) curves and areas under ROC curves indicate that good vessel detection performance can be achieved with a 40-MHz transducer for flow velocities ≥2 mm/s and with a 30-MHz transducer for flow velocities ≥1 mm/s. In the second part of the analysis, CPD was plotted as a function of wall filter cut-off velocity for each flow-phantom data set. Three distinct regions were observed: overestimation of CPD at low cut-offs, underestimation of CPD at high cut-offs and a plateau at intermediate cut-offs. The CPD at the plateau closely matched the phantom's vascular volume fraction and the length of the plateau corresponded with the flow-detection performance of the Doppler system assessed using ROC analysis. Color pixel density vs. wall filter cut-off curves from analogous in vivo experiments exhibited the same shape, including a distinct CPD plateau. The similar shape of the flow-phantom and in vivo curves suggests that the presence of a plateau in vivo can be used to identify the best-estimate CPD value that can be treated as a quantitative vascularity metric. The ability to identify the best CPD estimate is expected to improve quantification of angiogenesis and anti-vascular treatment responses with power Doppler. (E-mail: jlacefield@eng.uwo.ca)

Interframe Clutter Filtering for High Frequency Flow Imaging

This study investigates ‘interframe’ clutter filtering with a high frequency (HF) flow imaging system with the objective of improving the performance of HF microvascular imaging at high frame rates. An interframe filter exploits the correlation of tissue signals on the time scale of the frame rate and is, therefore, insensitive to tissue spectral broadening induced by sweeping a single element transducer over a region of tissue. In vitro experiments were conducted in a tissue-mimicking flow phantom over a range of mean flow velocities (0.5 to 70.0 mm/s). Power Doppler (PD) imaging and color flow (CF) imaging were performed for both slow (0.25 fps) and fast (20 fps) scanning acquisitions. Flow data acquired at 20 fps and interframe filtered had similar velocity and mean Doppler power values as the 0.25 fps single-frame filtered data sets. In vivo validation experiments were conducted using a 500 μm blood vessel in a human finger and detected blood flow of 2 to 3 mm/s. Further in vivo experiments examining experimental murine tumors demonstrated the feasibility of performing HF PD and CF imaging at high frame rates using interframe filtering. (E-mail: aneedles@swri.ca)

In vivo quantitation of tumour vascularisation assessed by Doppler sonography in rat mammary tumours

This study was designed to evaluate high-frequency power Doppler (PDS) and to quantify treatment-induced changes in an experimental autochtonous mammary tumour model in rats. A total of 13 rats with N-methyl, N-nitroso urea-induced mammary tumours were split into three courses; 6 rats were treated with epirubicin, 3 received a placebo injection and 4 had irradiation of their tumour with a direct electron beam using a single dose of 18 Gy. In all groups, treatment began when the tumour area reached at least 1 cm 2 and was preceded by the first power Doppler sonography study of the tumour (Echo #1). Echo #2 was carried out in the middle of the placebo or epirubicin treatment (after 3 weeks) or 7 days after irradiation in the irradiated group. Echo #3 was carried out at the end of placebo or epirubicin treatment or 28 days after irradiation. Then colour pixel density (CPD) and vascularity index (VI) were quantitated. Intraobserver and interobserver variability of the CPD and VI quantitation was low (r = 0.99 and 0.97, respectively, for intraobserver and interobserver variability of the CPD values). The monitoring of CPD and VI showed an increase with time during the observation period. No increase in CPD or VI was observed in treated mammary tumours ( p < 0.01). Power Doppler sonography quantitation of angiogenesis is reproducible, noninvasive and feasible in this in vivo breast cancer model. The monitoring of angiogenesis according to different treatments is feasible in real-time. Further studies are needed to investigate the predictive value of CPD and VI on sensitivity of mammary tumours to anticancer treatment. (E-mail:Tranquart@med.univ-tours.fr)

Intraoperative echocardiographic imaging of coronary arteries and graft anastomoses during coronary artery bypass grafting without cardiopulmonary bypass

Background: No accepted approach exists for the intraoperative evaluation of the quality of coronary arteries and the technical adequacy of graft anastomoses during coronary artery bypass grafting without cardiopulmonary bypass. Methods and Results: We assessed the accuracy of high-frequency epicardial echocardiography and power Doppler imaging in evaluating coronary arteries during coronary artery bypass grafting without cardiopulmonary bypass. To validate measurements of coronary arteries and graft anastomoses by high-frequency epicardial echocardiography and power Doppler imaging, we compared luminal diameters determined by these methods with diameters determined histologically in a study of off-pump coronary artery bypass grafting in 20 dogs. Technical errors were deliberately created in 10 grafts (stenosis group). The results of these animal validation studies showed that the maximum luminal diameters of coronary arteries and graft anastomoses measured by high-frequency epicardial echocardiography (HEE) and power Doppler imaging (PDI) correlated well with the histologic measurements: HEE = 1.027 × Histologic measurements + 0.005 (P <.0001); PDI = 0.886 × Histologic measurements + 0.0453 (P =.0001). Similar results were found in the evaluation of the stenosis group: PDI = 0.991 × Histologic measurements + 0.074 (P <.0001). Subsequently, we demonstrated the clinical applicability of this approach in 12 patients who underwent minimally invasive or off-pump coronary artery bypass grafting. Twenty graft anastomoses were examined intraoperatively by highfrequency epicardial echocardiography and power Doppler imaging, and luminal diameters determined by power Doppler imaging were compared with those determined by postoperative coronary angiography. The results demonstrated that graft anastomosis by power Doppler imaging correlated well with the angiographic measurements: PDI = 1.018 × Angiographic measurements – 0.106 (P <.0001). Conclusion: High-frequency epicardial echocardiography can provide meaningful information on the target coronary artery, and power Doppler imaging can accurately measure graft anastomoses and can detect technical errors and inadequacies during coronary artery bypass grafting without cardiopulmonary bypass.