Timing

The adage that "timing is everything" is certainly true for CE MRA. Since CE MRA depends substantially on Gd concentration, and contrast enhancement is a dynamic process, it is not surprising that vascular visualization relies heavily on timing-i.e. the moment in which imaging is actually performed [4-8]. With traditional extracellular Gd-chelate contrast agents, much of an intravenously administered dose will diffuse rapidly out of the vascular space into adjacent tissues within 5 minutes, thereby increasing background signal and reducing the vascular contrast-to-noise ratio (CNR).

In most instances, CE MRA is performed for arterial evaluation. As previously mentioned, arteries are best imaged if imaging data are acquired during peak arterial enhancement (i.e. when the concentration of Gd is greatest, see Fig. 2). The arrival time for the contrast bolus in the region of interest depends on the patient's cardiac output and the status of the intervening vascular anatomy. For example, the arrival of contrast agent into the iliac arteries might be significantly delayed in patients with congestive heart failure. Individual contrast arrival times can vary significantly. Peak contrast enhancement of the abdominal aorta, for example, has been shown to range from 10 seconds to as long as 60 seconds, with the longest delay occurring in a patient with inherently slow flow due to the presence of a large thoracoabdominal aneurysm [44].

Fundamental to the proper synchronization of arterial CE MRA is the acquisition of imaging data (specifically central k-space data, see below) during the period of preferential arterial enhancement prior to the occurrence of significant venous enhancement. This period varies with each vascular territory and can be quite short. For example in the carotid-jugular circulation it can be a mere 5 seconds [14,45] (Figs. 5, 6). Similarly, accurate timing is exceedingly important for CE MRA of the renal arteries due to the comparatively rapid enhancement of the renal veins.

Accurate determination of the appropriate delay time between contrast administration and image acquisition can therefore be challenging. Prior to the availability of MR compatible injectors and fast imaging methods, an empiric estimation of the bolus arrival time was used. This technique, also called "best guess" or "educated guess," used pre-determined times (e.g. a 10 second delay for CE MRA of the thoracic aorta and a 12 second delay for renal CE MRA) but generally required higher doses of Gd-chelate (e.g. 40 to 60 mL or 0.2 to 0.3 mmol/kg) to ensure sufficiently long arterial phase duration of an adequate Gd concentration [4,5].As mentioned above, peak arterial enhancement is highly variable between individual patients and is rarely estimated reliably on the basis of physiologic parameters alone [46]. Whereas CE MRA techniques based on fixed timing delays are frequently successful, these methods typically require higher doses of contrast agent - thereby, increasing study costs - and have an increased rate of failure. This is particularly evident for CE MRA of the carotid arteries [47] and renal arteries because the windows of preferential arterial enhancement are brief.

Tailoring CE MRA for individual variations in contrast arrival times by using a timing method,

Mra Coratids Images
Fig. 5. Delayed phase carotid 3D CE MRA. On this coronal MIP, significant enhancement of the jugular veins ("J") is seen because imaging was performed too late (i.e. after the period of preferential arterial enhancement). (Reprinted and adapted with permission from [7])
Sat Band Placement For Mra With Contrast

Fig. 6a-g. Carotid timing bolus scan. On axial fast spoiled gradient echo images (a-f) using a superior and inferior saturation bands, progressive enhancement of the carotid and vertebral arteries can be seen (compare top row with bottom row). Using an operator-defined region of interest, relative signal measurements in the carotid artery (arrow) and jugular vein (not shown) can be measured. Enhancement curves (g) can be plotted and the bolus arrival time can be estimated for CE MRA. In this case, the peak arterial enhancement of the test bolus occurs at 12 seconds. The preferential arterial phase window (i.e. period of selective arterial enhancement prior to venous contamination) is roughly 5 seconds. For optimum arterial depiction, the critical central k-space data should be timed to be acquired after 12 seconds but before significant venous enhancement (Reprinted and adapted with permission from [7])

Carotid Artery Test Bolus

Carotid Artery Test Bolus

Carotid Artery Assessment

on the other hand, will both minimize venous contamination and optimize arterial SNR and CNR resulting in improved diagnostic reliability and greater technical success rates. Moreover, by accurately timing the CE MRA examination, optimized arterial SNR and CNR can frequently be achieved with lower doses of contrast agent, thereby reducing overall examination costs. An additional benefit of using lower doses of contrast agent for CE MRA is that additional amounts can be used for other applications during the same examination period.

There are three methods for accurate timing. The most widely used method involves perform

Fig. 6a-g. Carotid timing bolus scan. On axial fast spoiled gradient echo images (a-f) using a superior and inferior saturation bands, progressive enhancement of the carotid and vertebral arteries can be seen (compare top row with bottom row). Using an operator-defined region of interest, relative signal measurements in the carotid artery (arrow) and jugular vein (not shown) can be measured. Enhancement curves (g) can be plotted and the bolus arrival time can be estimated for CE MRA. In this case, the peak arterial enhancement of the test bolus occurs at 12 seconds. The preferential arterial phase window (i.e. period of selective arterial enhancement prior to venous contamination) is roughly 5 seconds. For optimum arterial depiction, the critical central k-space data should be timed to be acquired after 12 seconds but before significant venous enhancement (Reprinted and adapted with permission from [7])

ing a test bolus scan to estimate the arrival of contrast in the target vascular bed [44-46]. This is usually achieved by administering a 1-2 mL dose of Gd-chelate contrast agent and measuring its arrival time in the vessel of interest. For optimal results it us advisable to administer the test bolus in a manner identical to that planned for the full dose during the CE MRA examination. Thus, it should be injected at the same rate and with sufficient saline flush (30 mL or more) to ensure that it arrives centrally and does not pool within the tubing set or a peripheral vein. Standardization of injections is easily afforded by use of an MR compatible injector.

Test bolus imaging should be performed using a fast two-dimensional (2D), T1-weighted spoiled gradient echo pulse sequence. Imaging parameters (e.g. repetition time, echo time, matrix, etc.) should be adjusted to yield a temporal resolution of approximately one image every 1-2 seconds. The field of view and matrix should also be adjusted to ensure proper visualization of the enhancing artery (e.g. aorta). If the intended image acquisition is perpendicular to the enhancing structure (e.g. axial for the abdominal aorta or carotid artery), then the use of inferior and superior saturation bands is recommended to minimize the normal signal variations that occur because of pulsatile inflow of spins (TOF effect) and to ensure that signal increases are due solely to the arrival of the contrast bolus. Image acquisition should be synchronized with the start of contrast agent injection. Thereafter the ideal contrast arrival time can be estimated based on the frame with the optimal arterial enhancement (Fig. 6).

More recently, real-time triggering for CE MRA has become commercially available. There are two main methods for real time synchronization of CE MRA. One early technique is referred to as automated bolus detection (e.g. MR SmartPrep, General Electric Medical Systems, Waukesha, WI, USA), in which monitoring for contrast bolus arrival and initiation of the MRA data acquisition are automated and integrated into a single pulse sequence [48-50]. This monitoring phase of the pulse sequence uses a high temporal resolution (400 msec) fast spin echo pulse sequence to monitor the arrival of contrast into an operator-defined volume of interest, typically a large vessel within the field of view. For example, the monitoring volume for a renal or abdominal CE MRA would be placed within the mid abdominal aorta. After a preliminary period (e.g. 10-20 sec) during which the baseline signal of the monitoring volume is determined, the pulse sequence informs the operator as to when to initiate the contrast administration

Mra Thoracic Aorta

Fig. 7a-d. Arterial phase 3D CE MRA of the thoracic aorta timed using MR fluoroscopic triggering. During the monitoring mode, two-dimensional MR fluoroscopic viewing of the contrast bolus progression (a, pre-contrast; b, pulmonary artery enhancement; c, thoracic aortic enhancement) is shown. Upon seeing the arrival of the bolus in the thoracic aorta, the operator prompts the patient to hold his or her breath and then triggers the 3D MRA data acquisition to begin. The 3D CE MRA (d, sagittal MIP) in this 71-year-old man with aortic regurgitation demonstrates a mildly dilated ascending aorta, which measured 4.2 cm in maximum diameter, and normal arch vessels but no aneurysm. High spatial resolution imaging was facilitated on this CE MRA by using a torso phased-array coil and SENSE image processing (Reprinted and adapted with permission from [7])

Fig. 7a-d. Arterial phase 3D CE MRA of the thoracic aorta timed using MR fluoroscopic triggering. During the monitoring mode, two-dimensional MR fluoroscopic viewing of the contrast bolus progression (a, pre-contrast; b, pulmonary artery enhancement; c, thoracic aortic enhancement) is shown. Upon seeing the arrival of the bolus in the thoracic aorta, the operator prompts the patient to hold his or her breath and then triggers the 3D MRA data acquisition to begin. The 3D CE MRA (d, sagittal MIP) in this 71-year-old man with aortic regurgitation demonstrates a mildly dilated ascending aorta, which measured 4.2 cm in maximum diameter, and normal arch vessels but no aneurysm. High spatial resolution imaging was facilitated on this CE MRA by using a torso phased-array coil and SENSE image processing (Reprinted and adapted with permission from [7])

while continuing its monitoring phase. Once the signal within the monitoring volume exceeds two pre-set thresholds (typically, two standard deviations and 20 percent rise over baseline signal), the pulse sequence automatically switches to its imaging phase. At the beginning of the imaging phase, the operator can also set a delay period (e.g. 3-5 sec) prior to the actual three-dimensional (3D) MRA data acquisition. The delay period provides an opportunity for the patient to initiate a breath hold prior to the actual 3D MRA data acquisition. A change in scanner sound (pitch) between the monitoring and imaging phases can serve as an audible cue for patients to alert them to the onset of the 3D MRA imaging acquisition.

The second method for real time CE MRA timing utilizes a fluoroscopic trigger (BolusTrak, Philips Medical Systems, Best, the Netherlands; Care Bolus, Siemens Medical Solutions, Erlangen, Germany; Fluoro Trigger, General Electric Medical Systems, Waukesha, WI, USA) [12,13,51]. Like the aforementioned automated triggering scheme, the real-time MR fluoroscopic technique also integrates a monitoring phase and an imaging phase into a single pulse sequence. However, with the MR fluoroscopic method, monitoring is performed by the operator visually using a continuous fast two-dimensional (2D) spoiled gradient echo pulse sequence with imaging centered over the vascular bed (Fig. 7). With this method, the operator is able to see the arrival of the contrast bolus and to manually initiate the imaging phase. Once again, a delay period can be selected to enable patient breath holding, which is generally preferable for most body applications.

All three methods for timing (test bolus scan, automated bolus detection and MR fluoroscopic trigger) permit reliable and time-efficient CE MRA acquisitions. For arteries such as the carotids in which very early enhancement of the veins occurs, bolus timing using a test bolus may provide good results without venous overlay even on scanners with less sophisticated gradient systems.

In general the actual method used varies from site to site, and typically depends on individual operator preference and equipment type. In all cases, however, it is important to ensure technical proficiency with the chosen method.

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