They are many instances when examination of low velocity blood flow in the abdomen can be of diagnostic importance. Detection of arterial flow in major arteries is not as technically difficult as that of small arteries such as in the renal cortex. Venous blood flow having a much lower velocity can prove difficult. Detection of portal blood flow is one example. Assessing organ parenchymal perfusion is a newer area under investigation in veterinary medicine. Low velocity blood flow occurs mainly in small veins, venules, and capillaries. The minimum detectable flow velocity is inversely dependent on the ultrasound frequency; when using a 2.5 MHz probe, the minimum detectable flow velocity is 1.5 cm/s. In addition, commercial Doppler devices are typically limited to the frequency below 15 MHz; the minimum detectable flow velocity is around 0.35 cm/s.
This presentation will concentrate on color, spectral and power Doppler techniques for diagnosis of selected diseases of the liver, spleen, kidney and lymph nodes. The use of contrast-enhanced harmonic ultrasound in these organs and its future potential in veterinary medicine will also be discussed.
Technical Factors for Optimizing Low Velocity Blood Flow Imaging
To accurately identify slow flow and not mistakenly consider flow to be absent, the Doppler parameters must be optimized for detection of slow flow. First, one must be sure that the B-mode parameters are optimized, including depth of field, location and number of focal zones, output power, and time-compensated gain. Spectral or power Doppler US is more sensitive in the detection of slow flow than is standard color Doppler flow US. The wall filter settings should be as low as possible so that low-frequency signals arising are not eliminated. The Doppler angle should be optimized, not only by correcting the angle with the computer, but by positioning the patient so as to allow the transducer to be placed in an appropriate superficial location. The strength of the color flow image decreases with the Doppler angle; if the angle is too small, the transducer should be moved to a more suitable position. In addition, the color box should be as small, narrow, and superficial as possible, whereas the gate used for pulsed Doppler sampling should be wide. A larger or wider box (i.e., greater depth) requires a longer round-trip time for pulses, reducing the PRF, increasing the signal processing time, degrading the image, and diminishing the ability to depict slow portal venous flow. The velocity range should be adjusted to a level appropriate for flow within the portal vein.
The velocity scale must be adjusted differently for high vs. low velocity flow. For examining low velocity flow and smaller vessels, a low PRF is required. Too high a PRF setting will not allow sampling of the lower velocity flows of veins and small vessels. If the PRF is not reduced, veins will appear to be void of flow and ischemia due to torsions, embolism or trauma could be falsely diagnosed. Neighboring veins and small arteries in other organs should be sampled to insure that the velocity scale settings are correct. For vessels with very slow flow (portal venous flow, splenic and mesenteric veins), a high filter setting may cause it to be inadvertently obscured or missed. Filters operate at variable frequencies to eliminate signal from low-velocity blood flow. To avoid the loss of signal that characterizes slow flow, filter settings should be kept at the lowest possible setting (typically in the 50-100-Hz range).
Under correction of the Doppler angle will result in a falsely low flow estimate. This may be of importance when examining a patient for portal hypertension where flow velocity within the portal veins is an important criterion. Increasing color Doppler gain to improve visualization of low flow vessels often can lead to noise artifacts, as these will also be enhanced by higher gain. These degrade the image making small vessels impossible to examine. For this reason, power Doppler allows improved visualization of small, low flow vessels that cannot be detected with color Doppler. Power Doppler (PD) is a technique in which a color map displays the integrated amplitude of the reflected Doppler signal from red blood cells. This technique is important since it allows detection of much lower flow velocities in small vessels, such as those in the renal cortex, when compared to CD. Since PD records only amplitude, gain can be increased more than with CD so that small vessels are seen without being degraded by noise.
The operator-adjusted gate defines the size and location of the area from which Doppler information is obtained. The gate should be as small as possible to exclude erroneous signal arising from adjacent vessels or marginal flow. Too large a gate may admit erroneous signal from adjacent vessels or may lead to acquisition of data from extraneous parenchyma. Too small a gate may give the false impression of reduced or even absent flow. For veins and small vessels, the gate should cover the lumen of the vessel but not larger than the vessel.
Practical Examples with Color, Spectral and Power Doppler
Renal Blood Flow
Hemodynamic alterations of the microcirculation of the vascular bed may well precede the clinical presence of renal disease. Ultrasound has become an increasingly important modality in the diagnosis of renal disease. Color and power Doppler now allow demonstration of the entire renovascular tree from the main renal arteries to the arcuate arteries as well as their terminal branches. For the detection of discrete losses of blood flow in the peripheral cortex, power Doppler has the advantage over color Doppler.1 CD and PD have also been used to detect blood flow in the renal allograft cortex in humans and to compare findings of flow alterations in the cortex with histologic diagnoses.2,3,4 In chronic transplant rejection in cynomolgus monkeys, it has been demonstrated that a reduction in cortical flow detected with power Doppler preceded the onset of arteriolar vasculopathy based on histology from serial biopsy sampling.5 It is generally considered that abnormal flow patterns are highly predictive for both rejection and acute tubular necrosis despite the non-specific nature of the findings.
Normal mesenteric vein flow is monophasic with slight undulations in maximal velocity. Mean portal flow velocity has been reported from 14.7 (+/- 2.5) to 18.1 (+/- 7.6) cm/s and maximal velocity at 32 cm/s. Portal hypertension occurs as a result of chronic liver disease or thromboembolism, stenosis or compression by enlarged hepatic lymph nodes or other masses. Portosystemic shunts are another cause. Posthepatic causes include compression of the hepatic veins, vena cava or right heart disease. Sonographic findings include reduced blood flow velocity, multiple tortuous varices (portal collaterals), chronic hepatic changes (small liver) and free abdominal fluid.
Splenic, Portal and Mesenteric Vein Thromboembolism
The absence of flow in a vein can be due to thromboembolism, external compression or neoplastic invasion. To detect subtle changes in echogenicity of the thrombus with gray-scale imaging, machine settings must be optimized and high frequency transducers are required. A recently formed thrombus is hypoechoic and can be difficult to detect. PRF and filter settings should be set as low as possible. These parameters increase the sensitivity for detecting low velocity flow. Sensitivity to low flow is also increased with higher Doppler frequencies. Recanalization may occur and be recognized as small color or power Doppler signals in and around the thrombus. Pulsed Doppler cranial to the thrombus will show absent or reduced flow. Color Doppler shows absence of flow within the venous lumen. Any absence of flow in color Doppler should be confirmed with power and spectral Doppler which have better sensitivity.
Veins within the abdomen have minimal resistance to flow and phasic changes occur in response to cardiac activity and changes in intraabdominal and intrathoracic pressures. Masses adjacent to the caudal vena cava, hepatic or renal veins can cause venous compression. Budd-Chiari syndrome is due to obstruction (compression or thrombosis) of the hepatic veins or caudal vena cava. Spectral and color Doppler will show reduced flow velocities and signals. Dilation of the veins can be seen with right heart failure, pulmonary hypertension, pericardial effusion, constrictive pericarditis, atrial tumor and tricuspid valve disease. The liver may be enlarged in all of these instances and ascites may be present. The typical Doppler wave form will be altered with reduced velocities towards the heart and possible increase in velocities away from the heart (atrial contraction).
Imaging Capillary Level Blood Flow with Contrast Harmonic Ultrasound
Contrast harmonic ultrasound is a new method of examining organ perfusion. Contrast harmonic ultrasound allows a study of the perfusion of lesions in a non-invasive manner and takes advantage of the properties of microbubble contrast media. At particular wavelengths unique to each contrast medium, resonance with the ultrasound beam occurs. This resulting distorted waveform has harmonic components. Because of this increased sensitivity of harmonic imaging, tissue perfusion on a capillary level can be detected using these media. Second generation ultrasound contrast agents are most commonly used now and are composed of perfluorocarbon-filled microbubbles, e.g., Definity®, and Optison®. Although occasional reactions have occurred in humans where their use is widespread and frequent (echocardiography) no adverse reactions have been reported in veterinary medicine. Special equipment and technical parameters are required to perform contrast harmonic ultrasound studies. Probes designed for recognizing harmonic signals from the contrast medium and special machine specifications are required. Sufficient energy (sound amplitude) must be provided to generate an adequate signal-to-noise ratio for agent detection, but not so high that bubble destruction occurs, preventing real-time display of perfusion. The mechanical indices or MI (mechanical index), frame rate, number and location of focal zones, and transmitted frequency must be carefully chosen for good study quality. Some manufacturers of ultrasound machines provide dedicated quantification software packages so that time-pixel intensity curves for organ perfusion can be assessed.
Practical Examples of CE Harmonic Ultrasound in Veterinary Medicine
Hepatic nodules are common findings in dogs and cats and their differentiation as benign or malignant requires invasive tissue sampling. The perfusion of liver in normal dogs has been described.6,7 The mean time to peak perfusion (TTP) varies from 22.9 to 46.3 s. There is no specific two-dimensional echo pattern for either benign or malignant nodules. Nodules are commonly found in normal large older dogs, which are the same age and breed distribution for high risk for developing neoplastic lesions. A recent study indicated that contrast ultrasound is highly accurate for prediction of benign or malignant based on perfusion patterns.8 Benign solid regenerative nodules appear isoechoic to the surrounding normal liver at peak normal liver perfusion. Hepatomas can appear more variable and have regions that are poorly perfused compared to the surrounding liver. Malignant nodules appear hypoechoic compared to the surrounding normal liver at peak normal liver perfusion. Neuroendocrine tumors may have an intense rim enhancement pattern in the later portion of the early phase of enhancement.
Contrast-enhanced color and power Doppler ultrasonography has been shown to be a promising tool to assess feline pancreatic disease.9 In comparison to normal cats, vascularity and perfusion was significantly increased in cats with pancreatic diseases. However, whether inflammatory diseases can be differentiated from benign hyperplasia or neoplasia by the means of contrast-enhanced color and power Doppler ultrasonography is yet to be determined. Because of its depth limitations, contrast enhanced color or power Doppler may not be used to assess the canine pancreas. Contrast-enhanced harmonic ultrasound of the canine pancreas has recently been described. Both the normal pancreas and the changes with pancreatitis have been investigated. Pixel intensities of the inflamed parenchyma are much greater than the normal pancreas and areas of perfusion voids can be detected in regions of necrosis. Anecdotally, there may be a correlation to extended hospital stay when perfusion void associated with necrosis are present.
Normal lymph nodes have primary afferent vessels which enter at the hilus, course centrally and branch symmetrically along the length of the node. The angioarchitecture of malignant lymphomatous nodes is different from this normal pattern based on contrast sonography.10 The majority of peripheral lymphomatous nodes had aberrant vessels adjacent to or beneath the lymph node capsule, and deviation of the hilus.
At present there is no perfusion or vascular characteristic which allows discrimination between splenic masses although normal perfusion has been defined.11 Smaller solid benign and malignant masses may have similar perfusion patterns as liver nodules. However, noninvasive differentiation of malignant splenic tumors from hematomas or benign nodules with contrast harmonic ultrasound would represent a valuable method since fine needle aspirates of splenic lesions are often nondiagnostic and tissue core biopsies may cause further bleeding. More work is currently ongoing in this field.
Contrast harmonic ultrasound has been established in normal dogs and has potential for recognizing pathology not possible with gray-scale and conventional color and power Doppler examinations. It provides a means of evaluating renal perfusion that is minimally invasive and applicable in a clinical setting.12 Fast early cortical perfusion is a reflection of the blood flow to the glomeruli. A delayed peak can be shown that may represent tubular perfusion in the second capillary bed concurrent with the more gradual inflow to the medulla.12 Diffuse diseases that affect the overall perfusion to the kidney could have an effect on one or more of the contrast perfusion parameters. These diseases may include trauma, shock, diffuse chronic glomerular or interstitial nephropathies, renal transplantation, and neoplasia.12 Similarly, focal or multifocal disease processes, including infarction, pyelonephritis, and neoplasia may affect contrast enhancement within the renal cortex.
Detecting small vascular alterations in infiltrative tissue and nodules may give clues to malignancy. Differences in vascularity and perfusion may play a role for the prognosis of various canine cancers. Cutaneous squamous cell carcinomas were highly vascularized and perfused in cats13, whereas vascularity and perfusion in fibrosarcomas was very low.14
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2. Sidhu MK, Gambhir S, Jeffrey RB, Jr., Sommer FG, Li KC, Krieger NR, Alfrey EJ, Scandling JD. Power Doppler imaging of acute renal transplant rejection. J Clin Ultrasound 1999;27(4):171-175.
3. Lu MD, Yin XY, Wan GS, Xie XY. Quantitative assessment of power Doppler mapping in the detection of renal allograft complications. J Clin Ultrasound 1999;27(6):319-323.
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12. Waller KR, O'Brien RT, Zagzebski JA. Quantitative contrast ultrasound analysis of renal perfusion in normal dogs. Vet Radiol Ultrasound 2007;48(4):373-377.
13. Ohlerth S, Laluhova D, Buchholz J, Roos M, Walt H, Kaser-Hotz B. Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography. Lasers Surg Med 2006;38(3):229-234.
14. Scharz M, Ohlerth S, Achermann R, Gardelle O, Roos M, Saunders HM, Wergin M, Kaser-Hotz B. Evaluation of quantified contrast-enhanced color and power Doppler ultrasonography for the assessment of vascularity and perfusion of naturally occurring tumors in dogs. Am J Vet Res 2005;66(1):21-29.