General Phases of Tissue Enhancement

General Phases of Tissue Enhancement

General phases of tissue enhancement is predominantly determined by the rate at which the contrast material is delivered and the time that elapses from the start of the injection and the time that elapses from the start of the injection and when scanning is initiated. The phases are frequently compared by the arteriovenous iodine difference (AVID). In practice this is done by comparing a Hounsfield Unit (HU) measurement taken within the aorta to that of a measurement taken in the inferior venacava. The radiographic attenuation in HU serves as a surrogate measure of iodine (i.e., contrast) concentration.

Three general phases of tissue enhancement are commonly discussed in CT:
The bolus phase (arterial)
The non-equilibrium phase (venous)
The equilibrium phase (delayed)

The bolus phase:
The bolus phase is that at which immediately follows an IV bolus injection. It is characterized by an attenuation difference of 30 or more Hounsfield Units between the aorta and the inferior venacava. In the bolus phase of contrast enhancement, the arterial structures are filled with contrast medium and brightly displayed on the image. Hence, this phase is also commonly called the arterial phase. Contrast media has not yet filled the venous structures. CT angiography images are taken while contrast is in the bolus phase.

The non-equilibrium phase:
The second phase is the non-equilibrium phase. It follows the bolus phase and is characterized by a difference of 10-30 HU AVID. The contrast agent is still much brighter in the arteries than in the parenchyma of organs, but now the venous structures are also opacified. Hence, it is also called the venous phase. This phase begins approximately one minute after the start of the bolus injection and lasts only a short time, approximately one minute. This window can be manipulated to some degree by varying conditions such as the volume and flow rate of the injected contrast medium. Most routine (non-angiographic) body images are acquired while contrast is in the non-equilibrium phase.

The equilibrium phase:
The last phase of tissue enhancement following the IV injection of contrast medium is known as the equilibrium or delayed phase. It can begin as early as 2 minutes after the bolus phase or following a drip infusion. In this phase, contrast media is largely emptied from the arteries, is greatly diluted in the veins and has soaked the organ parenchyma. In this phase, intravascular structures and interstitial concentrations of contrast material equilibriate and decline at an equal rate. It is characterized by an attenuation difference between aorta and the inferior venacava of less than 10 HU. The equilibrium phase is the worst phase for acquiring scans of the body, particular the liver. Compared with non-contrast exams, visualization of tumors in the liver is improved in both the bolus and non-equilibrium phases, but not in the equilibrium phase. In some instances scanning in the equilibrium phase is worse than simply scanning without IV contrast enhancement. Because in this phase, contrast material disperses more equally in the hepatic parenchyma and the tumor's interstitial space, the tumor can become isodense (i.e., the same density as the surrounding tissue) and be indistinguishable.

Table 1: Terms used to describe contrast phases and approximate times *
Phases
Seconds
Early arterial phase
15-25 sec
Late arterial phase
35-45 sec
Hepatic arterial phase
17-25 sec
Late hepatic arterial phase
40-55 sec
Portal venous phase
65-80 sec
Hepatic venous phase
75-80 sec
Early delayed hepatic phase (i.e., vascular equilibrium)
3-5 min
Late delayed hepatic phase (i.e., parenchymal equilibrium)
10-15 min
Parenchymal pancreatic phase
40-60 sec
Enteric phase
40-50 sec
Corticomedullary phase
45-70 sec
Nephrographic phase
80-180 sec
Excretory phase
>180 sec
*There is no consensus regarding the exact times after a bolus injection, these phases are reached. In addition, both injection parameters and patient factors will have a significant impact on when each of the phases occur.
The route that intravenously administered contrast medium takes from the site of injection to the various target organs is quite long. Along the way is a relatively predictable sequence of vascular and organ enhancement with various mixing processes. To mention just a few points along the way, the contrast material flows from the injection site vein into the venacava, enters the right atrium, pass the pulmonary circulation and finally arrive in the aorta. Along the way to the right atrium, the contrast mixes with opacified blood. Once the agent reaches the right ventricle, the mixing of opacified and non-opacified blood is complete. The contrast material enters the aorta during the arterial phase then passes through draining veins that either join the venacaba or enter the portal venous system. Contrast material in the portal system enhances the liver parenchyma (the organ's tissue; as opposed to the vascular structures) and drains into the liver veins before it reaches the right atrium again. As the contrast material flows back to the right heart from various organs, recirculation effects occur. Typical contrast arrival times for various organ systems are shown in Table 2:

Table 2: Contrast arrival times after injection into the right cubital vein
Region of Contrast Arrival
Time
Right atrium
6-12 sec
Main pulmonary artery
9-15 sec
Left atrium
13-20 sec
Aorta
15-22 sec
Carotids
16-24 sec
Renal arteries
18-27 sec
Femoral arteries
22-33 sec
Jugular vein
22-30 sec
Suprarenal IVC
24-32 sec
Infrarenal IVC
120-250 sec
Splenic vein
30-45 sec
Mesenteric veins
35-50 sec
Hepatic veins
50-80 sec
Femoral veins
120-250 sec

Circulation Time:
The circulation time is defined as the time taken for an indicator injected into the blood to pass between two measuring points in the blood stream. In healthy adults at rest, the circulation time from the cubital vein to the central arteries (carotid artery, abdominal aorta) is 13-22 seconds. Optimal opacification can be expected at the time of maximum concentration (peak time). Circulation times are dependent on the cardiac output.

Table 3: Circulation times (sec) in a healthy person
Measuring Points
Time
Arm-ear time
8-12 sec
Appearance time
13-22 sec
Peak time
15-28 sec
Lung-ear time
3-5 sec

Table 4: Circulation times (t) in pulse beats (n)
Measuring Points
Time
Arm-right ventricle
4 sec
Arm-left ventricle
11 sec
Arm-thoracic aorta
12 sec
Arm-abdominal aorta
13 sec
Arm-brain
13 sec
Arm-iliac arteries
15 sec
Where t=n60/f sec and f=heart rate (per min)


Arteriovenous transit time:
The arteriovenous transit time is defined as the interval between the times that the maximum contrast medium concentration enters the afferent artery of the organ and the time that it reappears in the efferent vein. The following values are based on circulatory measurements.

Table 5: Arteriovenous transit time
Organ
Time
Brain
6-8 sec
Kidney
8-12 sec
Lung
4-7 sec
Liver (hepatic artery)
10-15 sec
Liver (superior mesenteric artery)
15-30 sec

A mean transit time of 7 sec can therefore be assumed for the brain and of 10 sec for abdominal parenchymatous organs. The liver is a special case which is opacified sequentially by the hepatic artery and the branches of portal vein.

Table 6: Scanning Table
Start of scan for
Time
Right heart
4 sec
Left heart
11 sec
Thoracic aorta
12 sec
Abdominal aorta
13 sec
Iliac arteries
15 sec
Brain
22 sec

Renal phases:
Contrast enhancement typically reaches a near-peak in the aorta from 15-22 sec after the start of the injection. The time it takes to reach peak attenuation is affected by the cardiac output of the patient. As more contrast medium reaches the aorta, the aortic enhancement rises only slightly more, creating a type of plateau. The peak aortic enhancement is reached at the end of this phase when all the contrast has been delivered, then drops off dramatically. The plateau can be extended by adding a saline flush, which will push forward the contrast material left in the tubing and in the veins leading to the aorta. Scanning within this enhancement plateau is ideal for imaging the arteries. Because the true peak enhancement point is short-lived (often less than 2 seconds), variable, and difficult to predict, scanning protocols are most often designed so that images are acquired within the plateau (which typically lasts 10-15 sec) and not at the peak.

Most organs have an exclusively arterial blood supply. The peak organ enhancement for such organs (e.g., pancreas, bowel, bladder) occurs about 5-15 sec after peak aortic enhancement. The kidneys are an exception since their excretion of contrast medium must also be considered. Kidney scans are often acquired in the nephrographic phase, which is 80-100 sec after injection. This can be accomplished by incorporating a slight scan delay between scans of the liver and that of the kidney.
CT protocol for evaluation of the kidneys consists of both non-enhanced and contrast enhanced CT scans obtained in suspended respiration, to overcome the motion artifact.
Corticomedually phase
Nephrographic phase
Excretory phase

Corticomedullary phase:
This phase occurs between 30-70 seconds after the start of contrast administration. The corticomedullary phase begins as contrast matrial enters the cortical capillaries and peritubular spaces and filters into the proximal cortical tubules. Renal cortex can be differentiated from renal medulla at this state because 1) vascularity of the cortex is greater than that of the medulla, and 2) contrast material has not yet reached the distal aspect of the renal tubules. The resultant CT nephrogram has been termed as cortical nephrogram. Corticomedullary phase images should always be obtained when information about the renal vasculature is desired or when there is a possibility that a detected renal mass may represent an aneurysm or an arteriovenous malformation or fistula. Maximal opacification of the renal vein and arteries occurs during this phase, allowing confident diagnosis of tumor extension to the vein.

Nephrographic phase:
This begins as contrast material proceeds from the cortical vessels and extracellular-interstitial space and enters the loops of Henle and collecting tubules. A homogeneous or tubular nephrogram results in which corticomedullary differentiation is lost. The nephrographic phase starts about 80 sec and lasts upto 180 sec after the start of injection, and it offers the best opportunity for discrimination between the normal renal medulla and a renal mass. The nephrographic phase is the most valuable for detecting renal masses and characterizing indeterminate lesions.

Excretory phase:
Approximately 180 sec after the start of contrast injection, the excretory phase begins. The contrast material is excreted into the collecting system, so the attenuation of the nephrogram progressively decreases. This phase is occasionally helpful to better delineate the relationship of a centrally located mass with the collecting system. This phase is also useful for evaluating urothelial masses.

Density Scale:
The density scale is measured in Hounsfield Units (HU). The fixed points of the density scale are defined by air (=-1000HU) and water (=0HU) and are therefore independent of the tube voltage used. The various kinds of tissue vary within certain limits in relation the value of water, depending on the effective radiation energy employed, so that the tissue densities reported in the literature (in HU) must be regarded as standard values. In computerized tomography, the density units are usually directly proportional to the linear attenuation coefficients.

Table 7: HU values of various tissues
Tissue
Standard HU
Range HU
Fluids
Standard HU
Bone (compact)
>250

Blood
80±10
Bone (spongy)
130±100

Blood (venous)
55±5
Thyroid
70±10

Plasma
27±2
Liver
65±5
45±75
Exudates (>30g protein/L)
>18±2
Muscle
45±2
35-50
Transudate (