Chapter 33B Neuroimaging
Vascular Imaging: Computed Tomographic Angiography, Magnetic Resonance Angiography, and Ultrasound
Computed Tomographic Angiography
Methods
Helical CT scanner technology, providing uninterrupted volume data acquisition, can rapidly image the entire cerebral circulation from the neck to vertex of the head within minutes. Typical CT parameters use a slice (collimated) thickness of 1 to 3 mm with a pitch of 1 to 2, which represents the ratio of the table speed per rotation and the total collimation. Data are acquired as a bolus of iodinated contrast medium traverses the vessels of interest. For CTA of the carotid and vertebral arteries in the neck, the helical volume extends from the aortic arch to the skull base. Typical acquisition parameters are 7.5 images per rotation of the x-ray tube, 2.5-mm slice thickness, and a reconstruction interval (distance between the centers of two consecutively reconstructed images) of 1.25 mm. For CTA of the circle of Willis and proximal cerebral arteries, the data acquisition extends from the skull base to the vertex of the head. Typical acquisition parameters for this higher spatial resolution scan are 3.75 images per rotation, 1.25-mm slice thickness, and an interval of 0.5 mm. A volume of contrast ranging from 100 to 150 mL is injected into a peripheral vein at a rate of 2 to 3 mL/sec and followed by a saline flush of 20 to 50 mL. Adequate enhancement of the arteries in the neck or head is obtained approximately 15 to 20 seconds after injection of the contrast, although this may vary somewhat in each case. Image acquisition uses automated detection of bolus arrival and subsequent triggering of data acquisition. The resulting axial source images are typically post-processed for two-dimensional (2D) and three-dimensional (3D) visualization using one or more of several available techniques including multiplanar reformatting, thin-slab maximum-intensity projection (MIP), and 3D volume rendering. Recently introduced CT with 320 detector rows enables dynamic scanning, providing both high spatial and temporal resolution of the entire cerebrovasculature (4D CTA). The cervical vessels are imaged by acquisition of an additional spiral CT scan analogous to 64-detector row CT. Validated clinical applications of this advanced technique currently remain under investigation (Diekmann et al., 2010).
Limitations
Contrast-Induced Nephropathy
Careful consideration must be made for performing contrast-enhanced CT studies in patients with renal impairment. Exposure to all contrast agents may result in acute renal failure, called contrast-induced nephropathy (CIN), which is typically reversible but may potentially result in adverse outcomes. The incidence of renal injury appears to be associated with increased osmolality of contrast agents, which have been steadily declining with the newer generations of nonionic agents. Patients with a creatinine level above 1.5 gm/dL or estimated glomerular filtration rate below 60 mL/min/1.73m2 remain at a higher risk for developing CIN. Treatment for this condition relies on prevention of this disorder, and agents such as N-acetylcysteine and intravenous (IV) saline and/or sodium bicarbonate have been demonstrated to reduce the incidence of CIN. Avoidance of volume depletion and discontinuation of nonsteroidal antiinflammatory drugs, which may cause renal vasoconstriction, is recommended for patients prior to the procedure. Patients on hemodialysis are recommended to undergo dialysis as soon as possible afterwards to reduce contrast exposure (Asif and Epstein, 2004; Kim et al., 2010).
Metal Artifacts
Metallic implants such as clips, coils, and stents are generally safe for CT imaging, but it should be noted that they may lead to severe streaking artifacts, limiting evaluation. These artifacts occur because the density of the metal is beyond the normal range of the processing software, resulting in incomplete attenuation profiles. Several processing methods are available to reduce the artifact signal, and operator-dependent techniques such as gantry angulation adjustments and use of thin sections to reduce partial volume artifacts may help decrease this signal distortion. Generally, knowledge of the composition of metallic implants may help in determining the potential severity of artifacts on CT. Cobalt aneurysm clips produce much more artifact than titanium clips. For patients with stents, careful consideration must be made in evaluating stenosis, as these implants may lead to artificial lumen narrowing on CTA. The degree of artificial lumen narrowing decreases with increasing stent diameter. Lettau et al. evaluated patients with various types of stents and found that CTA may be superior to magnetic resonance angiography (MRA) at 1.5T for stainless steel and cobalt alloy carotid stents, whereas MRA at 3T may be superior for nitinol carotid stents (Lettau et al., 2009; van der Schaaf et al., 2006).
Applications
Extracranial Circulation
Carotid Artery Stenosis
In evaluating occlusive disease of the extracranial carotid artery, CTA complements conventional or digital subtraction angiography (DSA) and serves as an alternative to MRA (Fig. 33B.1). In the grading of carotid stenosis using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria, Randoux and colleagues (2001) found that the rate of agreement between 3D CTA and DSA was 95%. Relative to DSA (the reference standard), severe stenosis (70%-99%) was detected with a sensitivity and specificity of 100% and 100%, respectively, for CTA and 93% and 100%, respectively, for contrast-enhanced MRA (CE-MRA). In addition, CTA and CE-MRA were significantly correlated with DSA in depicting the length of the stenotic segment.
Other investigators have reported lower sensitivity (80%-89%) yet comparable specificity (96%-100%) for CTA in detecting severe stenosis (Binaghi et al., 2001; Magarelli et al., 1998). Those investigators found that time-of-flight (TOF) MRA had higher sensitivity (92%-93%) than CTA and similar specificity (98%-100%). Binaghi and colleagues also compared CTA with DSA and showed that the sensitivity was the same (89%), whereas specificity was higher for CTA (100%) than for DSA (81%). In 2006, Wardlaw et al., performed a meta-analysis on studies comparing CTA with DSA for the diagnosis of carotid artery stenosis. For detection of severe (70% to 99%) stenoses, CTA demonstrated a pooled sensitivity and specificity of 77% and 95%, respectively. Data for moderate (50%-69%) stenoses were determined to be sparse and unreliable (Wardlaw et al., 2006). An earlier systematic review found CTA to be a reliable method for detecting severe (70%-99%) stenoses, with a sensitivity and specificity of 85% and 93%, respectively. For detection of a complete occlusion, the sensitivity and specificity were 97% and 99%, respectively (Koelemay et al., 2004). Saba et al. evaluated the use of multidetector CTA and carotid ultrasound in comparison to surgical observation for evaluating ulceration, which is a severe complication of carotid plaques. CTA was found to be superior, with 93.75% sensitivity and 98.59% specificity compared to carotid ultrasound, which demonstrated 37.5% sensitivity and 91.5% specificity (Saba et al., 2007).
Fibromuscular dysplasia (FMD), which often involves a unique pattern of stenoses in the cervical vessels, may be detected by CTA, although no large studies have evaluated the sensitivity and specificity for detection. This disorder, which characteristically demonstrates a string-of-beads pattern of vascular irregularity on angiography, has been reliably demonstrated on carotid artery evaluations from case reports. This may potentially reduce the need for more invasive angiographic imaging in the future, although further studies in this area are required (de Monye et al., 2007).
Carotid and Vertebral Dissection
Dissections of the cervicocephalic arteries, including the carotid and vertebral arteries, account for up to 20% of ischemic strokes in young adults (Leys et al., 1995). CTA findings include demonstration of a narrowed eccentric arterial lumen in the presence of a thickened vessel wall, with occasional detection of a dissecting aneurysm. In subacute and chronic dissection, CTA has been shown to detect a reduction in the thickness of the arterial wall, recanalization of the arterial lumen, and reduction in size or resolution of dissecting aneurysm. CTA or MRA is superior to DSA in depicting the distal portions of the cervical internal carotid artery (ICA), a common site of dissection. CTA is likely superior to MRI alone in evaluating aneurysms at these sites because MRI findings are often complicated by the presence of flow-related artifacts. CTA depiction of dissections at the level of the skull base may be complicated in some cases because of to beam hardening and other artifacts that obscure dissection findings, including similarities in the densities of the temporal and sphenoid bones with the dissected ICA.
A retrospective review compared combined multidetector CT/CTA with MRI/MRA among 18 patients with 25 dissected vessels in both anterior and posterior circulations. CT/CTA was preferred for diagnosis in 13 vessels, whereas MRI/MRA was preferred in 1 vessel, and the techniques were deemed equal in the remaining 11 vessels. It should be noted that such combinations of noninvasive angiographic study with other CT or MRI components is common and therefore does not reflect the role of CTA or MRA alone. A significant preference for CT/CTA was noted for vertebral artery dissections but not for ICA dissections (Vertinsky et al., 2008). When compared with DSA, a small retrospective review of patients found that multidetector CTA had a sensitivity of 100% and specificity of 95% for detecting vertebral artery dissections (Pugliese et al., 2007). A small study evaluated multislice CTA with cervical axial T1-weighted MRI and MRA among seven patients with carotid artery dissection. The combination of MRI and MRA identified dissection in five of the seven patients that were identified by CTA. Additionally, a dissecting aneurysm was identified by CTA that was missed by MRI and MRA. These findings suggest that CTA may be at the very least a complementary study to provide additional information (Elijovich et al., 2006).
Intracranial Circulation
Acute Ischemic Stroke
Computed tomography angiography is a reliable alternative to MRA in evaluating arterial occlusive disease near the circle of Willis in patients with symptoms of acute stroke (Knauth et al., 1997; Shrier et al., 1997) (Fig. 33B.2). CTA shows clinically relevant occlusions of major cerebral arteries and enhancement caused by collateral flow distal to the site of occlusion. CTA may be superior to transcranial Doppler (TCD) ultrasound in diagnosing atherothrombotic MCA disease in Asian patients presenting with middle cerebral artery (MCA) stroke (Suwanwela et al., 2002). CTA detected MCA stenosis measuring more than 50% in twice as many patients as TCD. The difference resulted primarily from improved detection by CTA of distal M1 and M2 stenosis. Because half of the patients studied by Suwanwela and colleagues had distal M1 and M2 disease, the authors concluded that TCD should not be used to screen for MCA stenosis.
In the detection of intracranial steno-occlusive disease, Hirai and colleagues (2002) have shown that combined CTA and MRA provide substantially higher sensitivity, specificity, and accuracy than MRA alone. Review of the CTA depiction of vessels in conjunction with the 3D time-of-flight (TOF) MRA reduced the frequency of overestimation of stenosis when compared with MRA alone. In the identification of 50% or greater stenosis, the sensitivity, specificity, and accuracy for the combined CTA and MRA evaluation were 100%, 99%, and 99%, respectively, and the values for 3D TOF-MRA alone were 92%, 91%, and 91%, respectively. The grading of stenosis by the combined approach agreed with DSA grading in 98% of cases. In a retrospective review of their cases, the authors found that CTA did not always correctly delineate arterial lumina with circumferential calcification and the cavernous portion of the ICA. Nguyen et al. evaluated 475 vessel segments in 41 patients who received both CTA and DSA studies and found that for arterial occlusions, CTA had demonstrated 100% sensitivity and specificity. For detection of 50% or more stenosis, CTA had 97.1% sensitivity and 99.5% specificity. There was no difference observed in CTA accuracy for vessel segments in the anterior versus posterior circulation (Nguyen-Huynh et al., 2008). In a recent review of published studies, Latchaw et al. found that in comparison to conventional angiography, CTA demonstrated sensitivities ranging from 92% to 100% and specificities of 82% to 100% for the detection of intracranial vessel occlusion. The sensitivities for detection of intracranial stenoses range from 78% to 100%, with specificities of 82% to 100% (Latchaw et al., 2009). CTA is considered to be superior to TCD in detecting intracranial stenoses and occlusions, with a high false-negative rate noted for Doppler ultrasound. Studies also suggest that CTA has a higher sensitivity when directly compared with 3D TOF-MRA. Bash et al. found that CTA had a sensitivity of 98% while MRA had a sensitivity of 70% for detection of intracranial stenosis. The sensitivity for detecting occlusions on CTA was 100% and only 87% on MRA. Additionally, CTA was noted to superior to both MRA and DSA in detecting posterior circulation stenoses when slow or balanced flow states were present, possibly owing to longer scan time, which allows for more contrast to pass through a critical stenosis. Although previous studies noted decreased accuracy with the presence of atheromatous calcifications, the sensitivity and specificity of CTA for stenosis quantification were not compromised by this when appropriate window and level adjustments were made to account for the blooming artifacts that are frequently associated with heavy calcifications (Bash et al., 2005).
Computed tomography angiography source images (CTA-SI) may be used to provide an estimate of perfusion by taking advantage of the contrast enhancement in the brain vasculature that occurs during a CTA, possibly making it unnecessary to perform a separate CT perfusion study with a second contrast bolus. In normal perfused tissue, contrast dye fills the brain microvasculature and appears as increased signal intensity on the CTA-SI. In ischemic brain regions with poor collateral flow, contrast does not readily fill the brain microvasculature. Thus, these regions demonstrate low attenuation (Schramm et al., 2002). The hypoattenuation seen on CTA-SI correlate with abnormality on diffusion-weighted MRI (DWI) and have been found to be more sensitive than noncontrast CT scans for the detection of early brain infarction (Camargo et al., 2007). The sensitivity of CTA-SI and DWI when directly compared has been found to be similar in detecting ischemic regions, but DWI is better at demonstrating smaller infarcts and those in the brainstem and posterior fossa. Such findings may be useful for patients with symptoms of acute infarction who cannot undergo MRI (Latchaw et al., 2009).
In addition to perfusion status, CTA imaging may potentially be used for prognostication in patients undergoing acute stroke intervention. The 10-point Clot Burden Score (CBS) was devised as a semiquantitative analysis of CTA to help determine prognosis in acute stroke (Fig. 33B.3). The CBS subtracts 1 or 2 points each for absent contrast opacification on CTA in the infraclinoid internal carotid artery (ICA) (1), supraclinoid ICA (2), proximal M1 segment (2), distal M1 segment (2), M2 branches (1 each), and A1 segment (1). The CBS applies only to the symptomatic hemisphere. A CBS below 10 was associated with reduced odds of independent functional outcome (odds ratio (OR) 0.09 for a CBS of 5 or less; OR 0.22 for CBS 6 to 7; OR 0.48 for CBS 8 to 9; all versus CBS 10). The quantification of intracranial thrombus extent with the CBS predicts functional outcome, final infarct size, and parenchymal hematoma risk acutely. This scoring system requires external validation and could be useful for patient stratification in stroke trials (Puetz et al., 2008).
The Alberta Stroke Program Early CT Score (ASPECTS) is a 10-point analysis of topographic CT scan score used in patients with MCA stroke (Fig. 33B.4 and Box 33B.1). Segmental assessment of MCA territory is made, and 1 point is removed from the initial score of 10 if there is evidence of infarction in the following regions: putamen, internal capsule, insular cortex, anterior MCA cortex, MCA cortex lateral to insular ribbon, posterior MCA cortex, anterior MCA territory immediately superior to M1, lateral MCA territory immediately superior to M2 and posterior MCA territory immediately superior to M3. An ASPECTS score of 7 or less predicts worse functional outcome at 3 months as well as symptomatic hemorrhage. Puetz et al. sought to determine whether the ASPECTS scoring system could be applied to CTA-SI and combined with the CBS system for improved prognostication. A 10-point ASPECTS score based on CTA-SI and the 10-point CBS were combined to form a 20-point score for patients presenting acutely with stroke who received thrombolysis treatment. For patients with a combined score of 10 or less, only 4% were functionally independent, and mortality was 50%. In contrast, 57% of patients with scores of 10 or greater were functionally independent, and mortality was 10%. Additionally, parenchymal hematoma rates were 30% versus 8%, respectively (Puetz et al., 2010). A similar semiquantitative scoring system for CTA-SI was devised for patients presenting with acute basilar artery occlusion and termed the posterior circulation (pc)-ASPECTS (Fig. 33B.5). This 10-point scoring system subtracts 1 or 2 points each for areas of hypoattenuation in the left or right thalamus, cerebellum, or posterior cerebral artery (PCA) territory, respectively (1 point), or any part of the midbrain or pons (2 points). Median follow-up pc-ASPECTS was lower in patients with a CTA-SI pc-ASPECTS less than 8 compared with patients with a CTA-SI pc-ASPECTS of 8 or higher, respectively. Hemorrhagic transformation rates were 27.3% versus 9.5%, respectively, for patients who received thrombolysis. The results indicate that such analysis can predict a larger final infarct extent in patients with basilar artery occlusion. Larger prospective trials are required for validation, but the systematic acute evaluation of CTA along with CTA-SI may potentially be used to help guide future stroke treatments (Puetz et al., 2009).
Box 33B.1 Alberta Stroke Program Early CT Score*
Intracerebral Hemorrhage
Patients presenting acutely with intracerebral hemorrhage (ICH) within the first few hours of symptom onset are known to be at increased risk for hematoma expansion. However, only a fraction of such patients arrive at a hospital within this time frame, so alternative means of identifying potential hemorrhage expansion have been sought because it is an important predictor of 30-day mortality. One such prognostic marker has been identified on CTA: the spot sign, defined as a tiny, enhancing foci seen within hematomas, with or without clear contrast extravasation. A prospective study by Wada et al. of 39 consecutive patients with spontaneous ICH within 3 hours of symptom onset identified this sign in 33% of cases. Sensitivity was found to be 91%, and specificity was 89% for predicting hematoma expansion. In patients with the spot sign, mean volume change was greater, extravasation was more common, and median hospital stay was longer (Wada et al., 2007).
A larger retrospective analysis determined that the presence of three or more spot signs, a maximum axial dimension of 5 mm or greater, and maximum attenuation of 180 Hounsfield units or more were independent predictors of significant hematoma expansion (Delgado et al., 2009). In another study, Delgado et al. noted that the presence of any spot sign increased the risk of in-hospital mortality (OR, 4.0) and poor outcome among survivors at 3-month follow-up (OR, 2.5). This was determined to be an independent predictor of both measures. The spot sign currently requires further validation but remains a promising use of CTA in guiding acute ICH management (Delgado et al., 2010).
Brain Death
The absence of cerebral circulation is an important confirmatory test for brain death, and CTA is emerging as an important alternative means of testing. A novel 4-point score was devised, with points subtracted based on the lack of opacification of the cortical segments of the MCAs and internal cerebral veins. Frampas et al. used this system to prospectively evaluate 105 patients who were clinically brain dead and found a sensitivity of 85.7% and specificity of 100%. This appears to be a possible alternative means of detecting cerebral circulatory arrest, and given that it is a fast and noninvasive technique, it may become a useful confirmatory test (Frampas et al., 2009; Escudero et al., 2009).
Cerebral Venous Thrombosis
The diagnosis of cerebral venous thrombosis (CVT) was previously often made with conventional angiography and more recently by MRI techniques. Magnetic resonance venography (MRV) is commonly considered the most sensitive noninvasive test in diagnosing CVT. However, given the prolonged imaging time and often limited availability, CTA has been studied as a potential alternate means of detecting CVT. Spiral CT with acquisition during peak venous enhancement has been implemented with single-section systems but remains limited in spatial and temporal resolution. One study directly comparing CTV with MRV demonstrated a sensitivity and a specificity of 75% to 100%, depending on the sinus or venous structure involved (Khandelwal et al., 2006). Multidetector-row CTA (MDCTA) offers higher spatial and temporal resolution, which allows for high-quality multiplanar and 3D reformatting. Two recent small studies found 100% specificity and sensitivity with MDCTA when compared to MRV. The venous sinuses could be identified in 99.2% and the cerebral veins in 87.6% of cases. MDCTA may be equivalent to MRV in visualizing cerebral sinuses, but further studies are needed to evaluate the diagnostic potential of MDCTA in specific types of CVT such as cortical venous thrombosis, thrombosis of the cavernous sinus, and thrombosis of the deep cerebral veins. The advantages of MDCTA include the short exam duration and the possible simultaneous visualization of the cerebral arterial and venous systems with a single bolus of contrast. MDCTA visualizes thrombus via contrast-filling defects and remains less prone to flow artifacts. A potential problem with this technique lies in the fact that in the chronic state of a CVT, older organized thrombus may show enhancement after contrast administration and may not produce a filling defect, leading to a false-negative result. The addition of a noncontrast CT with the MDCTA is sometimes used to remove another potential to obtain false-negative results from the presence of a spontaneously hyperattenuated clot that could be mistaken for an enhanced sinus. This phenomenon is known as the cord sign and may be seen in 25% to 56% of acute CVT cases (Gaikwad et al., 2008; Linn et al., 2007).
Cerebral Aneurysms
Although 3D TOF-MRA and dynamic 3D CE-MRA have similar sensitivity and specificity to CTA for detection of intracerebral aneurysms at least 5 mm in diameter, they have lower sensitivity for aneurysms smaller than 5 mm (Villablanca et al., 2002; White et al., 2001) (Figs. 33B.6 and 33B.7). The results of the International Study of Unruptured Intracranial Aneurysms (ISUIA) (Wiebers et al., 2003) suggest that MRA, despite its lower sensitivity for smaller aneurysms, would not significantly change management, because incidental aneurysms smaller than 10 mm should not be treated (exceptions may be made for individuals with daughter aneurysm formation, a family history of subarachnoid hemorrhage, and young patients). However, in general, the accuracy of CTA is felt to be at least equal if not superior to that of MRA in most circumstances, and in some cases, its overall accuracy approaches that of DSA (Latchaw et al., 2009).
Using optimized helical CTA acquisition and post-processing protocols that included 3D volume-rendered images, 3D thick-slab and grayscale 2D single-section images, and thick-slab multiplanar reformatted 2D images, Villablanca and colleagues (2002) reported a sensitivity for the detection of small aneurysms (<5 mm diameter) of 98% to 100%, compared with 95% for DSA. The specificity of both CTA and DSA was 100%. CTA image analysis times ranged from 6 to 36 minutes (mean, 16 minutes). The smallest aneurysm detected was 1.9 × 1.6 × 1.3 mm3, and 48% of aneurysms were detected in the presence of subarachnoid hemorrhage. The sensitivity of CTA exceeded that of DSA, primarily because the optimal projection necessary to visualize some aneurysms could be displayed on the post-processed CTA images but was not or could not be displayed by the 2D DSA. Other disadvantages of DSA that have been noted by investigators include superimposition of normal vessels, obscuring a small aneurysm, and the lack of an internal image scale for estimating the aneurysm sac and neck dimensions. Villablanca et al. (2002) showed that CTA can provide quantitative information such as dome-to-neck ratios and aneurysm characterization such as the presence of mural thrombi or calcium, branching pattern at the neck, and the incorporation of arterial segments in the aneurysm. The 3D images in particular provided a surgically useful display of the aneurysm sac in relation to skull base structures (see Fig. 33B.7). The authors concluded that clinically relevant aneurysms can be detected by CTA using published protocols, routine scanners, and commercially available image-processing workstations. Furthermore, CTA can be a reliable source of information for treatment planning.
Cerebral veins show much more anatomical variation than arteries. The presence of an unexpected vein or the lack of collateral drainage from a region drained by a vein that may need to be sacrificed during surgery can alter the approach to resection of an aneurysm. Kaminogo and colleagues (2002) used 3D CTA to demonstrate the venous anatomy accurately. They showed the usefulness of this information in selecting a therapeutic procedure (surgery versus endovascular coiling) and in planning the approach for surgical treatment.
Recent data indicate that CTA is a safe and accurate imaging technique for evaluating most extracranial and intracranial vessels to detect the presence of stenoses or occlusions, as well as for the detection of intracranial aneurysms. The accuracy of CTA appears equal to or superior to MRA imaging in most circumstances, and its accuracy sometimes approaches that of DSA. The development of new advanced CT scanners with more detectors may further enhance the accuracy of this technique (Latchaw et al., 2009).
Magnetic Resonance Angiography
Methods
Contrast-enhanced MRA (CE-MRA) uses scan parameters that are typical of 3D TOF-MRA but uses gadolinium to overcome the problem of saturation of the slow-flowing blood in structures that lie within the 3D slab (Fig. 33B.8). The scan time per 3D volume is on the order of 5 to 10 minutes, and data are acquired in the first 10 to 15 minutes after the bolus infusion of a gadolinium contrast agent (0.1-0.2 mmol/kg). Presaturation bands usually are ineffective at suppressing the downstream signal from vessels when gadolinium is present. In 3D CE-MRA (called fast, dynamic, or time-resolved CE-MRA), the total scan time per 3D volume (usually about 30-50 partitions) is reduced to 5 to 50 seconds (Fain et al., 2001; Melhem et al., 1999; Turski et al., 2001). Data are acquired as the bolus of the gadolinium contrast agent (0.2-0.3 mmol/kg and 2-3 mL/sec infusion rate) passes through the vessels of interest, taking advantage of the marked increase in intravascular signal (first-pass method). Vessel signal is determined primarily by concentration of injected contrast, analogous to conventional angiography. Because 3D CE-MRA entails more rapid data acquisition, and hence higher temporal resolution, than TOF-MRA, spatial resolution may be reduced. The most common approaches to synchronizing the 3D data acquisition with the arrival of the gadolinium bolus in the arteries are measurement of the bolus arrival time for each patient using a small (2 mL) test dose of contrast followed by a separate synchronized manual 3D acquisition (Foo et al., 1997) by the scanner operator (Fain et al., 2001; Foo et al., 1997). Another method rapidly and repeatedly acquires 3D volumes (<10 sec per volume) in the neck, beginning at the time of contrast bolus injection to ensure that at least one 3D volume showing only arteries will be acquired (Turski et al., 2001). Subtraction of preinjection source images from arterial phase images, termed digital subtraction MRA, is sometimes used to increase vessel-to-background contrast.
Fig. 33B.8 3T contrast-enhanced magnetic resonance angiography (CE-MRA) of the cerebrovascular system.
The advent and increasing availability of MRI scanners with 3.0 tesla (T) or even higher field strengths (up to 7T) in selected centers may also be used to improve MRA by capitalizing on higher signal-to-noise ratios and parallel imaging (Nael et al., 2006; Pruessmann et al., 1999). Parallel imaging at 3T or greater can be used to improve spatial resolution, shorten scan time, reduce artifacts, and increase anatomical coverage in first-pass CE-MRA. Recent investigation with 7T TOF-MRA demonstrated that such ultrahigh field strength allows vivid depiction of the large vessels of the circle of Willis with significantly more first- and second-order branches and can even distinguish diseased diminutive vessels in hypertensive patients (Hendrikse et al.; 2008; Kang et al., 2009; Kang et al., 2010). The 4D time-resolved MRA (4D MRA) is a novel contrast-enhanced vascular imaging method under investigation that uses novel processing techniques to achieve subsecond temporal resolution while maintaining high spatial resolution. Dynamic MRA scans may be obtained up to 60 times faster and with higher spatial resolution at 3T. The resulting images may attain the diagnostic performance of conventional DSA, allowing for better characterization of various vascular lesions (Hope et al., 2010; Parmar et al., 2009; Willinek et al., 2008).
Limitations
Nephrogenic Systemic Fibrosis
Clinicians should be aware that a rare but serious complication of contrast-enhanced MRI studies includes the development of nephrogenic systemic fibrosis (NSF).This condition is characterized by widespread thickening and hardening of the skin, with the potential for rapid systemic progression and immobility over several weeks. Although the precise mechanism remains unclear, NSF was first noted in 1997 and occurs exclusively in patients with renal failure. The majority of reported cases involved exposure to a gadolinium chelate within 2 to 3 months prior to disease onset in dialysis-dependent patients. A large percentage of cases has been specifically associated with gadodiamide (Omniscan), with a possible dose-dependent effect, although it should be noted that cases have been reported with all gadolinium agents. Careful consideration must be made for gadolinium administration in patients with renal impairment (glomerular filtration rate <30 mL/min/1.73m2), especially those on dialysis. The risks and benefits should be carefully discussed prior to any contrast-enhanced procedures, and the dose of gadolinium should be minimized. Additionally, for patients on hemodialysis, prophylactic dialysis is generally recommended as soon as possible, ideally within 3 hours after contrast administration (Kuo et al., 2007).
Metal Implant Contraindications
Limitations due to the presence of metallic materials (clips, stents, coils) remains a common concern in patients undergoing vascular imaging. Aneurysm clips made from martensitic stainless steels remain a contraindication for MRI procedures, because excessive magnetic forces may displace these implants and cause serious injury. However, most clips are now made of metals that are non-ferromagnetic, and all patients with any metallic implants require screening to determine whether they are safe to undergo an MRI study. For the majority of coils and stents that have been tested, it is unlikely that these implants would become moved or displaced as a result of exposure to MRI systems operating at 1.5T or even 3T. Additionally, it is often unnecessary to wait an extended period of time after a procedure to perform an MRI study in a patient with an implant made of non-ferromagnetic material unless there are concerns associated with MRI-related heating. Dental materials including wires and prostheses do not appear to pose a risk, although they may result in artifact on MRI. Artifacts from metal may have varied appearances on MRI related to the type or configuration of the piece of metal. Artifact sizes may increase at 3T compared to 1.5T, depending on the implant type and composition, but these distortions may be substantially reduced by optimizing imaging parameters. Patients who are deemed unsafe for MRI upon screening may be considered for CT evaluation (Olsrud et al., 2005; Shellock, 2002).
Applications
Extracranial Carotid and Vertebral Circulation
Time-of-Flight Mra
Earlier clinical reports outlined the advantages and pitfalls of TOF-MRA for imaging of the extracranial circulation and estimation of degree stenosis at the carotid bifurcation (Norris and Rothwell, 2001). The degree of stenosis tends to be overestimated by the traditional 2D TOF-MRA method. A corollary of this observation is that a 2D TOF study with normal or near-normal findings effectively excludes the possibility of severe (70% to 99%) stenosis. The most accurate results are obtained when short TE and small voxel size are used. Second, a consensus estimate of stenosis derived from a combination of the 2D and 3D TOF methods results in greater specificity than 2D TOF alone. This improvement results primarily from the inclusion of the 3D TOF method, in which stenosis is less likely to be overestimated, particularly if original (Fig. 33B.9) or reformatted source images are evaluated rather than the MIP images. In the combined TOF approach, the 2D TOF method is used primarily to distinguish slow flow from occlusion and, in general, the combined TOF approach is considered superior to DSA in differentiating high-grade stenosis from occlusion. A flow gap, which is a segmental dropout of signal from the carotid (or other vessels) caused by intravoxel phase dispersion or saturation, is often taken as a sign of stenosis measuring 70% or more. This association should be viewed with caution, however, because in one published series of patients, flow gap was observed with the 2D TOF technique at sites of 50% to 60% stenosis as determined by DSA.
Third, in detecting stenosis appropriate for carotid endarterectomy, TOF-MRA is less sensitive than DSA (75% MRA, 87% DSA) but more specific (88% MRA, 46% DSA); however, when stenosis estimates by TOF-MRA and DSA are concordant and are then taken together, the combined MRA and DSA examination is more sensitive (96%) and specific (85%) than either study alone. Furthermore, when patients are classified as to whether carotid endarterectomy is indicated by the noninvasive examination and then judged against the results of DSA, the misclassification rate for the concordant MRA and DSA results is much lower than that of either test alone (MRA and DSA 7.9%, MRA 18%, DSA 28%) (Johnston and Goldstein, 2001). Therefore, surgical decisions are more likely to be correct when based on concordant TOF-MRA and DSA results.
Three-Dimensional Contrast-Enhanced Mra
Compared with 2D and 3D TOF-MRA, 3D CE-MRA delineates carotid arterial stenosis better (Willig et al., 1998) (Fig. 33B.10). Surface morphology (e.g., ulcerated plaque) and nearly occluded vessels (e.g., “string sign”) are more easily identified, and arterial occlusions are more confidently identified. Severe carotid bifurcation stenosis may be detected by 3D CE-MRA with high sensitivity (93%-100%) and specificity (88%-96%) (Huston et al., 1998; Johnson et al., 2000; Lenhart et al., 2002; Remonda et al., 2002; Wutke et al., 2002) using DSA as the standard method of diagnosis. TOF techniques yield similar results to 3D CE-MRA for mild to moderate stenosis, thus obviating time spent on CE-MRA setup and processing. Advantages of 3D CE-MRA include greater anatomical coverage (Fig. 33B.11). For high-grade stenosis, which can cause intravascular flow gaps on TOF MIP images, the addition of CE-MRA to the imaging protocol provides sensitivity and specificity equivalent to CTA in determining the severity of stenosis (relative to DSA as the reference standard).
TOF-MRA and CE-MRA have been found to achieve high accuracy for the detection of high-grade ICA stenoses and occlusions, with CE-MRA having slight benefit over TOF-MRA. A systematic review and meta-analysis of 37 TOF-MRA studies and 21 CE-MRA studies was performed by Debrey et al. and found that for the detection of high-grade (≥70-99%) ICA stenoses, TOF-MRA had an overall sensitivity of 91.2%, with a specificity of 88.3%. The sensitivity of CE-MRA was higher at 94.6%, with a specificity of 91.9%. For the detection of complete ICA occlusions, the sensitivity of TOF-MRA was 94.5%, and the specificity was 99.3%, while CE-MRA demonstrated a sensitivity of 99.4% and specificity of 99.6%. However, for moderately severe ICA stenoses (50%-69%), sensitivity was found to be poor in TOF-MRA and only fair in CE-MRA studies. TOF-MRA had a sensitivity of only 37.9% and a specificity of 92.1%, while CE-MRA had a sensitivity of 65.9% with a specificity of 93.5% (Debrey et al., 2008).
The ability to detect an FMD pattern of stenoses by MRA in the carotid vessels remains uncertain. This disorder may not be as well delineated on TOF-MRA owing to limited resolution, although no large comparative studies with CE-MRA have been performed. In one series evaluating FMD in the renal arteries, Willoteaux found the sensitivity and specificity of CE-MRA to be 97% and 93%, respectively. These findings suggest that using CE-MRA to identify FMD in the cervical vessels may be possible, although further studies are required (Willoteaux et al., 2006).
Atherosclerotic narrowing of the vertebral artery commonly involves the origin or distal intracranial portion. For TOF-MRA evaluation of posterior-circulation cerebrovascular disease, the vertebral origins usually are not evaluated for the same reasons the common carotid origins are not evaluated. Typically, a 3D TOF study covering the vertebrobasilar system from the C2 level to the tip of the basilar artery is done (Fig. 33B.12). However, sequential 2D TOF-MRA of the neck is useful in determining whether proximal occlusion is present and in demonstrating flow direction in the vertebral arteries in patients with suspected subclavian steal. A 2D TOF study obtained with no presaturation band shows flow enhancement in both vertebral arteries, whereas a study obtained with a superiorly located walking presaturation band shows flow only in the vertebral artery with normal anterograde flow. The 3D CE-MRA techniques can display both the origins and distal intracranial portions of the vertebral arteries in a single acquisition and are particularly useful in evaluating vertebral artery segments with partial or complete signal loss caused by slow flow and in-plane saturation effects. The accuracy of 3D CE-MRA measurements of stenosis at the vertebral artery origin has yet to be reported, although the accuracy is unlikely to equal that of carotid bifurcation measurements because of the smaller size of the vertebral origins (Kollias et al., 1999). Nevertheless, an analysis of the elliptical centric encoding technique predicts that it can achieve an isotropic spatial resolution of 1 mm (before zero filling) in a field of view typically used for bilateral carotid and vertebral imaging (Fain et al., 1999). Stenosis or occlusion of the subclavian artery is now routinely evaluated with 3D CE-MRA.