Contrast enhanced vascular three-dimensional ultrasound imaging.

In other imaging modalities three-dimensional (3D) data displays are well established; not so in ultrasound. Due to the real-time requirements of ultrasound the time available to compute 3D displays is limited, particularly when flow data is acquired with Doppler techniques. Consequently, it is only recently that improvements in computer processing power have resulted in useful vascular 3D ultrasound scans. Many manufacturers have now implemented free-hand 3D power Doppler capabilities on their scanners. However, to obtain flow signals from smaller vessels associated e.g., with tumor neovascularity, may very well require the introduction of a microbubble based ultrasound contrast agent into the blood stream. Given the up to 30 dB enhancement of Doppler signals produced by the contrast microbubbles quite spectacular vascular 3D images are feasible. Moreover, new contrast imaging techniques, such as harmonic imaging, have now permitted 3D vascular information to be acquired and displayed in grayscale with the associated improvement in resolution. In this paper we will review different aspects of contrast enhanced vascular 3D ultrasound imaging including implementation, contrast specific techniques and in vivo imaging.

Indirect MR arthrography of the knee: effects of low-intensity ultrasound on the diffusion rate of intravenously administered Gd-DTPA in healthy volunteers.

RATIONALE AND OBJECTIVES: To evaluate whether application of low-intensity ultrasound may increase the diffusion rate of intravenously administered gadopentetate dimeglumine (Gd-DTPA) and increase the amount of joint fluid on indirect magnetic resonance (MR) arthrography. METHODS: Conventional MR imaging, indirect MR arthrography, and power Doppler ultrasonography were performed before and after application of therapeutic, pulsed low-intensity ultrasound in 12 asymptomatic knees of 12 volunteers. Intra-articular diffusion of intravenously administered Gd-DTPA as measured by signal intensity differences of the intra-articular joint fluid before and after ultrasound treatment was assessed. In addition, the amount of joint fluid was rated, and differences in synovial blood flow as evidenced by power Doppler ultrasonography were noted. RESULTS: All volunteers tolerated well the application of therapeutic low-intensity ultrasound. A significant increase in intra-articular diffusion of intravenously administered Gd-DTPA was noted in all knees, and an increase in joint fluid was noted in 8 of 12 knees (66.6%). Detection of power Doppler flow signal in the synovium of the suprapatellar recess was possible in one instance at posttreatment exam. CONCLUSIONS: Use of pulsed, therapeutic low-intensity ultrasound may increase the diffusion rate of intravenously administered Gd-DTPA and may induce joint effusion.

The role of contrast-enhanced sonography for radiofrequency ablation of liver tumors.

OBJECTIVE: To assess the feasibility and usefulness of contrast-enhanced sonography for tumor detection and guidance of liver VX2 tumor ablation and to evaluate post radiofrequency ablation effectiveness. METHODS: VX2 tumors were implanted into the livers of 6 rabbits. Both conventional and harmonic gray scale and power Doppler imaging were performed with a commercially available scanner to evaluate the liver tumors before and after intravenous injection of a sonographic contrast agent before and after radiofrequency ablation. Contrast-enhanced imaging was used to detect the tumors before ablation, to guide needle insertion, and to measure the ablation sites after radiofrequency ablation. Pathologic examination was performed for comparison. RESULTS: Three tumors were seen without contrast enhancement, whereas 10 tumors (<1 cm) were detected with contrast enhancement. Intentionally, 2 tumors were completely ablated and 5 tumors were partially ablated. In 3 cases, incompletely ablated tumors could only be identified on contrast-enhanced Doppler imaging by enhancing the detection of residual tumor vascularity. There was excellent concordance between sonographic imaging and gross pathologic findings. CONCLUSIONS: Contrast-enhanced sonographic imaging appears useful for detection of liver tumors and for guiding and monitoring tumor ablation therapies.

Blood flow estimation with harmonic Flash Echo Imaging.

Blood volume flow estimation remains an important task for the functional evaluation of internal organs. In vitro and in vivo flow estimation has been carried out using Flash Echo Imaging in harmonic mode after the administration of microbubble-based ultrasound contrast agents. The in vitro flow volume rate correlated with the constant replenishment level but less so with the video intensity decay rate. The in vivo volume flow rates obtained in four dogs agreed well with CVI-Q (time domain correlation) based flow measurement. Our experimental results indicate that the volume flow rate can be accurately estimated in vitro and in vivo using harmonic Flash Echo imaging.

Ultrasound of the ankle and foot.

Ultrasound is an excellent tool for evaluating common ankle problems. it is more economical than MRI and its real-time nature helps in correlating the study with the symptomatic area. US can be used in ankle to evaluate tendons (including tears, tendinitis and tenosynovitis), joints, plantar fascia, ligaments, soft tissue masses, ganglion cysts, Morton's neuroma, and to look for foreign bodies. Power Doppler can be used to evaluate blood flow in acute inflammatory process and in reflex sympathetic dystrophy.

Gray scale second harmonic imaging of acoustic emission signals improves detection of liver tumors in rabbits.

This study evaluates a new reticuloendothelium specific sonographic contrast agent NC100100 (Sonazoid) for detection of liver VX-2 tumors in rabbits. Gray scale imaging of five groups of three rabbits, with hepatic VX-2 tumors implanted 7, 10, 12, 14, and 18 days previously, was performed prior to injection of Sonazoid (dosages, 0.01-0.5 ml/kg). Sonazoid produces induced acoustic emission after uptake in the liver. Therefore, harmonic gray scale images were obtained immediately after injection as well as delayed (by up to 2(1/2) h). Five rabbits (one from each group) also had angiography performed, while all animals were evaluated by pathologic examination. Non-contrast enhanced sonography detected 17 of 61 tumors (29%), as well as three false-positives, while the addition of Sonazoid detected 57 tumors (93%) and one false-positive (P<0.001). Acoustic emission made 2 x 2 mm tumors (invisible in conventional B-mode sonography) clearly perceivable in harmonic gray scale. In the subgroup that received angiography, 12 of 36 tumors (33%) were detected with conventional sonography compared to 22 tumors (61%) seen with angiography (P = 0.002). After injection of Sonazoid the ultrasonographic detection rate increased to 97% (35 of 36 tumors), which was a significant improvement over angiography (P = 0.00024). Improved detection of hepatic VX-2 tumors with second harmonic gray scale imaging of Sonazoid is possible because of this agent's acoustic emission capabilities.

Comparison of fundamental and wideband harmonic contrast imaging of liver tumors.

Wideband harmonic imaging (with phase inversion for improved tissue suppression) was compared to fundamental imaging in vivo. Four woodchucks with naturally occurring liver tumors were injected with Imagent (Alliance Pharmaceutical Corp., San Diego, CA). Randomized combinations of dose (0.05, 0.2 and 0.4 ml/kg) and acoustic output power (AO; 5, 25 and 63% or MI < or = 0.9) were imaged in gray scale using a Sonoline Elegra scanner (Siemens Medical Systems, Issaquah, WA). Tumor vascularity, conspicuity and contrast enhancement were rated by three independent observers. Imagent produced marked tumor enhancement and improved depiction of neovascularity at all dosages and AO settings in both modes. Tumor vascularity and enhancement correlated with mode, dose and AO (P < 0.002). Fundamental imaging produced more enhancement (P < 0.05), but tumor vascularity and conspicuity were best appreciated in harmonic mode (P < 0.05). Under the conditions studied here, the best approach was wideband harmonic imaging with 0.2 ml/kg of Imagent at an AO of 25%.

Shear rate estimation using a clinical ultrasound scanner.

Wall shear stress is a factor in the development of atherogenesis, thrombus formation, and embolization, but its existence is very difficult to determine with ultrasonography. Instead, we estimated shear rates using a clinical ultrasound scanner and compared results from vessels with and without stenoses. Velocity profiles were obtained from color M-mode images on a P700 scanner. Maximum shear rates were calculated off-line as the maximum velocity gradients. In vitro, studies were performed on a flow phantom with a vessel containing a 50% stenosis. Shear rates within the stenosis were significantly higher than those obtained outside the stenosis (P < 0.00001) and varied more than the peak velocities. In vivo, the internal carotid artery of 10 volunteers and 13 patients (with stenoses) was studied. The mean shear rate was 414 s(-1) +/- 154.5 s(-1) in normal vessels and 687 s(-1) +/- 263.5 s(-1) in stenotic vessels (P = 0.00017). In conclusion, shear rate estimates can be obtained with a clinical ultrasound scanner from color M-mode images. Shear rates estimated in vessels with stenoses are significantly higher than those obtained in normal vessels in vitro as well as in vivo.

Effect of filling gases on the backscatter from contrast microbubbles: theory and in vivo measurements.

Two surfactant-based contrast agents, ST44 and ST68, were produced according to US Patent # 5,352,436 and filled with either air, C4F10 (perfluorobutane) or SF6 (sulfur hexaflouride). Ten rabbits received i.v. injections of each agent/gas combination with 5 repetitions of each dose (range: 0.005-0.13 mL/kg). A custom-made 10-MHz cuff transducer was placed around the surgically exposed distal aorta and audio Doppler signals were acquired in vivo. Quantitative in vivo dose responses were calculated off-line using spectral power analysis and compared to a theoretical model of microbubble dissolution and enhancement. For qualitative comparisons, 10 rabbits were imaged pre- and postcontrast administration (dose: 0.1 mL/kg) in gray-scale and colour. All agent/gas combinations produced marked Doppler enhancement with air bubbles enhancing least of all (p < 0.0001) and ST68-SF6 best of all (maximum: 27.6 +/- 2.04 dB; p < 0.012). There were no significant differences between other agent/gas combinations (0.30 < p < 0.70). Theoretical enhancement was within 1 order of magnitude of the experimental observations (i.e., deviations of up to 10 dB). The duration of contrast enhancement was 1-2 min for air-filled bubbles, 3-5 min for SF6-filled bubbles and more than 7 min for C4F10-filled bubbles. In conclusion, ST68-SF6 microbubbles produced most in vivo enhancement of the agent/gas combinations studied. Theory matched the measurements within an order of magnitude.

Tissue-specific US contrast agent for evaluation of hepatic and splenic parenchyma.

PURPOSE: To evaluate the recently developed ultrasonographic (US) contrast agent SHU 563A, which is specifically taken up by the reticuloendothelial system (RES). MATERIALS AND METHODS: Color Doppler imaging (CDI) was performed in a gel phantom, with SHU 563A microbubbles in stationary suspension. CDI was performed in vivo in five woodchucks with natural hepatomas and in 12 rabbits before and after intravenous bolus injections of SHU 563A (0.16-0.48 mL/kg). After a 15-135-minute delay, the liver and spleen were scanned again, and the image findings were compared with pathologic analysis results. RESULTS: Phantom CDI demonstrated a random mosaic color pattern in spite of the lack of flow. This phenomenon, which is associated with bubble rupture, is termed induced acoustic emission. In vivo, delayed imaging demonstrated acoustic emission signals in normal parenchyma, whereas no mosaic color was seen in regions lacking reticuloendothelial cells (e.g., tumors). Four of 12 VX-2 tumors detected with pathologic analysis were detected with US alone; the remaining eight tumors were detected by using US with contrast agent (100%, P = .0078). Nine of 20 hepatomas were detected at baseline US, whereas 17 were detected after administration of SHU 563A (P = .0215). Acoustic emission enabled detection of hepatic tumors as small as 3 mm in diameter. CONCLUSION: CDI with SHU 563A demonstrates a random mosaic color pattern, even without flow. The characteristic appearance of acoustic emission signals provides a distinctive method of visualizing normal hepatic tissues and substantially improves the detectability of hepatic tumors.

Conventional and hypobaric activation of an ultrasound contrast agent.

Hypobaric activation is a new injection technique for use with the contrast agent EchoGen and, in this study, the agent's ability to produce parenchymal enhancement in vivo, with and without prior hypobaric activation, was investigated. Injections, ranging in dose from 0.05 to 0.5 mL/kg, were administrated through a peripheral vein to eight woodchucks with multiple hepatomas. At the 0.10 mL/kg dose level, seven of eight injections following hypobaric activation (88%) resulted in definite parenchymal enhancement. Conversely, dosages of 0.10 mL/kg without prior hypobaric activation produced no grey-scale changes. Only at the 0.4 and 0.5 mL/kg dosage level did the conventional administration technique obtain similar results (4 of 5 injections increased the echogenicity for a 0.4 mL/kg dose). These differences were statistically significant (p = 0.031). In vitro experiments were conducted to establish the physical mechanisms behind hypobaric activation. Relative measurements of contrast microbubble sizes were performed with a phase Doppler particle analyzer after hypobaric and after conventional (bolus) activation. Hypobaric activation produced approximately 20 times more microbubbles per unit volume than the conventional method. In conclusion, this investigation has demonstrated the benefits of prior hypobaric activation when performing in vivo contrast studies with EchoGen and determined the physical mechanisms behind this new injection technique. Hypobaric activation of EchoGen increases contrast enhancement and reduces dose size.

Increased soft-tissue blood flow in patients with reflex sympathetic dystrophy of the lower extremity revealed by power Doppler sonography.

OBJECTIVE: We evaluated the ability of power Doppler sonography to show increased soft-tissue blood flow in patients with reflex sympathetic dystrophy of the lower extremity. SUBJECTS AND METHODS: Power Doppler sonography was performed in 30 patients with reflex sympathetic dystrophy of the lower extremity and in 26 asymptomatic control subjects. The bilateral power Doppler sonograms that were obtained of the soft tissues of the dorsum of the foot of each subject were grouped in pairs, and three sonologists who were unaware of clinical information independently reviewed the images. Images were evaluated for the amount of power Doppler signal shown on the following scale: 1 = no flow or minimal flow; 2 = mild flow; 3 = moderate flow; and 4 = marked flow. RESULTS: More power Doppler flow was seen in the patients with reflex sympathetic dystrophy than in the control subjects (p < .005). In addition, side-to-side asymmetry of flow was seen in patients, but this trend was not statistically significant (p < .20). Receiver operating characteristic (ROC) analysis showed that combined flow and asymmetry were more related to reflex sympathetic dystrophy than either parameter alone (area under the ROC curve: for flow, 0.748; for asymmetry, 0.566; for both, 0.799). We found that when the sum of power Doppler flow in both feet was greater than or equal to five, and asymmetry of flow was greater than or equal to one, the sensitivity of power Doppler sonography for reflex sympathetic dystrophy was 73% and the specificity was 92%. CONCLUSION: Patients with reflex sympathetic dystrophy of the lower extremity have increased power Doppler flow compared with asymptomatic control subjects. Patients may also exhibit more side-to-side asymmetry of flow than control subjects.

Color Doppler sonographic detection of tumor flow in superficial melanoma metastases: histologic correlation.

Color Doppler sonographic detection of tumor flow within superficial melanoma metastases was investigated to determine if tumor size, vessel size, or vessel number influences signal detection. Color Doppler imaging of 32 pathologically proved melanoma metastases was performed at 6 MHz with color Doppler imaging parameters optimized for each lesion scanned. All lesions were measured in three dimensions and the presence or absence of internal flow was documented. Seven surgically excised metastases underwent immunohistochemical staining for endothelial markers. Internal flow was detected in 21 of 32 masses and was completely absent in 11. In comparison to all masses without flow, the masses with flow had significantly greater anteroposterior dimensions (P < 0.00036) and volumes (P < 0.01). Histologically, mean vessel diameter in masses with flow was significantly greater (P < 0.05) than in those without flow, but mean vessel number was not significantly different. In conclusion, detectability of tumor blood flow in superficial melanoma metastasis may be related more to tumor size and vessel size than vessel number. Failure to detect color signal within a superficial melanoma mass does not indicate a lack of internal vascularity.

Superficial melanoma metastases: appearances on gray-scale and color Doppler sonography.

OBJECTIVE: The purpose of this study was to describe the sonographic appearances of melanoma metastases of the skin, subcutaneous tissues, and superficial lymph nodes. MATERIALS AND METHODS: Gray-scale sonography was performed on 31 superficial melanoma metastases in 18 patients. Discreteness of borders, contours, echogenicity, echotexture, and degree of acoustic through-transmission were evaluated for each lesion. Color Doppler sonography was also performed on 25 of the 31 lesions, by which the amount of internal color flow was qualitatively assessed. RESULTS: Twenty-eight (90%) of the 31 metastases had well-defined borders. Contours were smooth in 17 (55%), lobulated in 12 (39%), and spiculated in two (6%). Nineteen metastases (61%) were hypoechoic to muscle, 10 (32%) were isoechoic, and two (6%) were hyperechoic. Echotexture was homogeneous in six lesions (19%), mildly heterogeneous in 13 (42%), moderately heterogeneous in 11 (35%), and markedly heterogeneous in one (3%). Twenty-two lesions (71%) showed enhanced acoustic through-transmission. Of the 25 melanoma metastases for which we performed color Doppler sonography, 18 (72%) had internal arterial color flow and seven (28%) did not. The flow was characterized as mild in 13 (72%) of 18, moderate in four (22%), and marked in one (6%). CONCLUSION: On sonography, superficial melanoma metastases typically are well-defined hypoechoic lesions with smooth or lobulated contours, mild to moderate heterogeneity, and enhanced acoustic through-transmission. Internal flow revealed by color Doppler sonography is present in many, but not all, superficial melanoma metastases.

Sonographic guidance for the localization of peripheral pulmonary nodules during thoracoscopy.

OBJECTIVE: The value of sonographic guidance during video-assisted thoracoscopic surgery (VATS) was studied in 13 patients with one or more peripheral pulmonary nodules who later underwent wedge resection. SUBJECTS AND METHODS: After a review of the chest radiographs and CT scans of each patient, sonographic guidance for VATS was requested by the attending surgeon when the nodule or nodules in question were determined to be too small or too deep in the lung parenchyma from the pleural surface for location by VATS. A multifrequency (5.0-, 6.5-, or 7.5-MHz) sonographic probe was introduced through a thoracoscopic port during VATS. The nodule or nodules in question were located by intraoperative sonography or determined by inspection and confirmed by sonography before wedge resection. The size and location of each lesion and the time needed for sonographic guidance were recorded. RESULTS: Sonography revealed a peripheral pulmonary nodule in 12 of the 13 patients. Of these, it confirmed the suspected location of the pulmonary nodule in six. In the remaining six patients, the surgeon was unable to locate the nodule without the use of sonography. The additional operative time required for sonographic guidance during VATS averaged 7.5 min. However, the time commitment of radiology personnel during surgery varied and was sometimes lengthy (maximum, 150 min). CONCLUSION: Sonographic guidance during thoracoscopy helped to locate lesions and determine their size and proximity to pleural surfaces. Sonographic guidance can be done safely and can be completed expeditiously. Unlike percutaneous hookwire techniques, sonographic guidance does not require an additional invasive procedure to locate the peripheral pulmonary nodule.

On the feasibility of real-time, in vivo harmonic imaging with proteinaceous microspheres.

Harmonic imaging is a new contrast-specific imaging modality, which utilizes the nonlinear properties of microbubble-based sonographic contrast agents by transmitting at the fundamental frequency but receiving at the second harmonic frequency. The feasibility of improving the detection of slow, small-volume blood flow using real-time harmonic imaging has been investigated in vivo. Proteinaceous microspheres (FS069) were administrated to four dogs, two woodchucks (with multiple hepatomas), and one rabbit. Three different scanners were used to obtain real-time images of kidneys and liver (including vessels) in harmonic and conventional gray scale and color flow modes. The duration of contrast enhancement lasted significantly longer in harmonic than in conventional modes (on average 87 s; P = 0.008). Harmonic images were less susceptible to artifacts, such as acoustic shadowing, and a clear increase in the (flow) signal-to-noise ratio was observed. These preliminary in vivo results demonstrate the feasibility of performing real-time, contrast-enhanced harmonic imaging, but further studies are required to establish clinical efficacy.

Laparoscopic liver sonography: preliminary experience in liver metastases compared with CT portography.

This study evaluated the ability of laparoscopic ultrasonography to detect, localize, and characterize focal liver masses. Laparoscopic ultrasonography and CT portography of the liver were performed in 13 patients with known or suspected malignancy. Laparoscopic ultrasonography directly influenced surgical management in four (31%) cases; three by detection of small focal masses and one by exclusion of masses suspected on CT portography. Laparoscopic ultrasonography provided guidance for biopsy or added important anatomic information in three cases. Laparoscopic ultrasonography was complementary to CT portography but added no additional information in three cases, and it failed to provide any information in two cases. Laparoscopic ultrasonography was falsely negative in one case. In this preliminary series, laparoscopic ultrasonography assisted surgeons in critical decision-making by either providing important new information, clarifying questionable areas, or complementing CT portography.

Malignant melanoma: impact of superficial US on management.

PURPOSE: To evaluate the impact of superficial ultrasonography (US) on clinical management of melanoma. MATERIALS AND METHODS: Superficial US in areas at high risk for local recurrence or nodal metastases was performed in 33 patients with cutaneous melanoma. Impact categories were assigned to each US study (n = 55): category 3, US added information that altered clinical management; category 2, US added information that did not change management; category 1, no added information and management unchanged; category 0, not helpful or was misleading. RESULTS: Twenty-two US studies (40%) were category 3: detection of nonpalpable metastases altered surgical therapy (n = 2), demonstration of pharmacodynamic response to chemotherapy (n = 5), and determination of benignancy or malignancy (n = 15). Nine (16%) were category 2: identification of nonpalpable metastases did not alter management. Twenty-two (40%) were category 1: supported clinical impression of no metastases (n = 18) or helped confirm cutaneous, subcutaneous, or nodal metastases (n = 4). Two (4%) were category 0: missed proved metastases. CONCLUSION: Superficial US affected management of melanoma by allowing detection and characterization of masses, guidance of biopsy, and assessment of pharmacodynamic response.

Parenchymal enhancement and tumor visualization using a new sonographic contrast agent.

The purpose of this study was to assess the ability of a sonographic contrast agent to increase parenchymal echogenicity and improve tumor visibility. The agent is an emulsion that changes at body temperature from nonechogenic submicrometer liquid droplets to echogenic 1 to 5 microns microbubbles, capable of transversing the pulmonary and capillary circulations. Peripheral venous injections (dosages of 0.05 to 0.8 ml/kg) were administered to five woodchucks (three with multiple hepatomas), 12 rabbits (with renal VX-2 tumors), and four dogs. Ultrasonograms were acquired from kidney, liver, tumors (including tumor vessels) and normal vessels. Uptake and washout curves were generated via videodensitometry. Finally, Doppler shifts from a cuff transducer around the celiac trunk were analyzed to provide an in vivo dose-response curve. Vascular enhancement, including hepatoma and VX-2 tumor vessels, was seen for 2 to 3 min. Maximum enhancement was 18.7 dB for a 0.6 ml/kg dose. Enhancement of normal liver and kidney parenchyma was observed in all three species for up to 20 min. Small hepatomas became more echogenic centrally, but larger tumors showed no increase in central echogenicity. In conclusion, improved tumor visibility and parenchymal enhancement was demonstrated in animals.

Synovial fluid in the hindfoot and ankle: detection of amount and distribution with US.

PURPOSE: To determine the amount and distribution of synovial fluid detectable with ultrasonography (US) of the hindfoot and ankle in asymptomatic volunteers. MATERIALS AND METHODS: US was performed with a 7.5- or 10-MHz linear transducer of 60 hindfeet and ankles in 30 volunteers. Presence and amount of fluid were assessed in the ankle joint recesses, adjacent bursae, and tendon sheaths. Symmetry of bilateral fluid was evaluated. RESULTS: Fluid was detected in the anterior recess in 20 ankles (bilaterally in eight volunteers), retrocalcaneal bursa in 30 ankles (bilaterally in 12 volunteers), posterior tibial tendon sheath in 46 ankles (bilaterally in 19 volunteers), and common peroneal tendon sheath in seven ankles (bilaterally in three volunteers). No fluid was seen in the posterior recess. On average, symmetry was present for only the retrocalcaneal bursal and peroneal tendon sheath fluid. CONCLUSION: US of the hindfoot and ankle commonly depicts articular, bursal, and tendon sheath fluid in asymptomatic volunteers. The presence of fluid in these locations, even when unilateral or asymmetric, does not necessarily imply underlying abnormality.