Chapter 416: Neuroimaging in Neurologic Disorders

Numerous noninvasive imaging options are available to clinicians evaluating patients with neurologic disorders. These include computed tomography (CT) and variations CT angiography (CTA), perfusion CT (pCT), and dual energy CT and magnetic resonance (MR) imaging (MRI) and variations MR angiography (MRA), MR vessel wall imaging, functional MRI (fMRI), MR spectroscopy (MRS), MR neurography (MRN), diffusion and diffusion tensor MR imaging, susceptibility-weighted MR imaging (SWI), arterial spin label imaging (ASL) and perfusion MRI (pMRI). Furthermore, a number of interventional neuroradiologic techniques have matured including catheter embolization, stent retrieval thrombolysis, aneurysm coiling and stenting, as well as numerous techniques for spine disorders, including CT myelography, fluoroscopy and CT-guided transforaminal and translaminar epidural and nerve root injections, radiofrequency ablation and blood patches. Multidetector CTA (MDCTA) and gadolinium-enhanced MRA techniques have reduced the need for catheter-based angiography, which is now reserved for patients in whom small-vessel detail is essential for diagnosis or for whom concurrent interventional therapy is planned (Table 416-1).

In general, MRI is more sensitive than CT for the detection of lesions affecting the peripheral and central nervous system (CNS), particularly those of the spinal cord, cranial nerves, and posterior fossa structures. Diffusion MR, a sequence sensitive to the microscopic motion of water, is the most sensitive technique for detecting acute ischemic stroke of the brain or spinal cord, and it is also useful in the detection and characterization of encephalitis, abscess, Creutzfeldt-Jacob disease, cerebral tumors and acute demyelinating lesions. CT, however, is acquired quickly, making it a pragmatic choice for patients with acute changes in mental status, suspected hemorrhage, and acute intracranial or spinal trauma. CT is also more sensitive than MRI for visualizing fine osseous detail and is indicated in the initial imaging evaluation of conductive hearing loss as well as lesions affecting the skull base and calvarium. MR may, however, add important diagnostic information regarding bone marrow infiltrative processes that are difficult to detect on CT.

TECHNIQUE

The CT image is a cross-sectional representation of anatomy created by a computer-generated analysis of the attenuation of x-ray beams passed through a section of the body. As the x-ray beam, collimated to the desired slice width, rotates around the patient, it passes through selected regions in the body. X-rays that are not attenuated by body structures are detected by sensitive x-ray detectors aligned 180° from the x-ray tube. A computer calculates a “back projection” image from the 360° x-ray attenuation profile. Greater x-ray attenuation (e.g., as caused by bone), results in areas of high “density” (whiter) on the scan, whereas soft tissue structures that have poor attenuation of x-rays, such as organs and air-filled cavities, are lower (blacker) in density. The resolution of an image depends on the radiation dose, the detector size, collimation (slice thickness), the field of view, and the matrix size of the display. A modern CT scanner is capable of obtaining sections as thin as 0.5–1 mm with 0.4-mm in-plane resolution at a speed of 0.3 s per rotation; complete studies of the brain can be completed in 1–10 s.

Multidetector CT (MDCT) is now standard. Single or multiple (from 4 to 320) solid-state detectors positioned opposite to the x-ray source result in multiple slices per revolution of the beam around the patient. In helical mode, the table moves continuously through the rotating x-ray beam, generating a continuous “helix” of information that can be reformatted into various slice thicknesses and planes. Advantages of MDCT include shorter scan times and thus reduced patient and organ motion, and the ability to acquire images dynamically during the infusion of intravenous contrast, the basis of CTA and CT perfusion (Figs. 416-1B and C). CTA is displayed in three dimensions to yield angiogram-like images (Figs. 416-1C, 416-2E and F, and see Fig. 420-3).

Intravenous iodinated contrast is used to identify vascular structures and to detect defects in the blood-brain barrier (BBB) that are caused by tumors, infarcts, and infections. In the normal CNS, only vessels and structures lacking a BBB (e.g., the pituitary gland, choroid plexus, and dura) enhance after contrast administration. While helpful in characterizing mass lesions as well as essential for the acquisition of CTA studies, the decision to use contrast material should always be considered carefully as it carries a small risk of allergic reaction and adds additional expense.

INDICATIONS

CT is the primary study of choice in the evaluation of an acute change in mental status, focal neurologic findings, acute trauma to the brain and spine, suspected subarachnoid hemorrhage, and conductive hearing loss (Table 416-1). CT often is complementary to MR in the evaluation of the skull base, orbit, and osseous structures of the spine. In the spine, CT is useful in evaluating patients with osseous spinal stenosis and spondylosis, but MRI is often preferred in those with neurologic deficits. CT is often acquired following intrathecal contrast injection to evaluate for spinal and intracranial cerebrospinal fluid (CSF) fistula, as well as the spinal subarachnoid space (CT myelography) in failed back surgery syndromes.

COMPLICATIONS

CT is safe, fast, and reliable. Radiation exposure depends on the dose used but is normally between 2 and 5 mSv (millisievert) for a routine brain CT study. Care must be taken to reduce exposure when imaging children, who are typically best studied with MR. With the advent of MDCT, CTA, and CT perfusion, the benefit must be weighed against the increased radiation doses associated with these techniques. Advances in postprocessing software now permit acceptable diagnostic CT scans at 30–40% lower radiation doses.

The most frequent complications are those associated with use of intravenous contrast agents. While two broad categories of contrast media, ionic and nonionic, are in use, ionic agents have been largely replaced by safer nonionic compounds.

Contrast nephropathy is rare. It may result from hemodynamic changes, renal tubular obstruction and cell damage, or immunologic reactions to contrast agents. A rise in serum creatinine of at least 44 μmol/L (0.5 mg/dL) within 48 h of contrast administration is often used as a definition of contrast nephropathy, although there is no accepted definition and other causes of acute renal failure must be excluded. The prognosis is usually favorable, with serum creatinine levels returning to baseline within 1–2 weeks. Risk factors for contrast nephropathy include age (>80 years), preexisting renal disease (serum creatinine exceeding 2 mg/dL), solitary kidney, diabetes mellitus, dehydration, paraproteinemia, concurrent use of nephrotoxic medication or chemotherapeutic agents, and high contrast dose. Patients with diabetes and those with mild renal failure should be well hydrated prior to the administration of contrast agents; careful consideration should be given to alternative imaging techniques such as MRI, noncontrast CT, or ultrasound (US). Nonionic, low-osmolar media produce fewer abnormalities in renal blood flow and less endothelial cell damage but should still be used carefully in patients at risk for allergic reaction. Estimated glomerular filtration rate (eGFR) is a more reliable indicator of renal function compared to creatinine alone because it takes into account age, race, and sex. In one study, 15% of outpatients with a normal serum creatinine had an estimated creatinine clearance of ≤50 mL/min/1.73 m² (normal is ≥90 mL/min/1.73 m²). The exact eGFR threshold, below which withholding intravenous contrast should be considered, is controversial. The risk of contrast nephropathy is minimal in patients with eGFR >30 mL/min/1.73 m²; however, the majority of these patients will only have a temporary rise in creatinine. The risk of dialysis after receiving contrast significantly increases in patients with eGFR <30 mL/min/1.73 m². A creatinine of 1.6 in a 70-year-old, non-African-American male corresponds to an eGFR of ~45 mL/min/1.73 m². The American College of Radiology suggests using an eGFR of 30 mL/min/1.73 m² as a threshold below which iodinated contrast should not be given without serious consideration of the potential for contrast nephropathy. If contrast must be administered to a patient with an eGFR <30 mL/min/1.73 m², the patient should be well hydrated, and a reduction in the dose of contrast should be considered. Use of other agents such as bicarbonate and acetylcysteine may reduce the incidence of contrast nephropathy.

Suggested guidelines for creatinine testing prior to contrast administration:

If serum creatinine is not available, it should be performed IF the patient has ANY of the following risk factors:

• Age >60

• History of “kidney disease” as an adult, including tumor and transplant

• Family history of kidney failure

• Diabetes mellitus treated with insulin or other prescribed medications

• Hypertension

• Paraproteinemia syndromes or diseases (e.g., myeloma)

• Collagen vascular disease (e.g., SLE, scleroderma, rheumatoid arthritis)

• Solid organ transplant recipient

If creatinine testing is required, a creatinine level within the prior 6 weeks is sufficient in most clinical settings.

Allergy

Immediate reactions following intravenous contrast media occur through several mechanisms. The most severe reactions are related to allergic hypersensitivity (anaphylaxis) and range from mild hives to bronchospasm and death. The pathogenesis of allergic hypersensitivity reactions is thought to include the release of mediators such as histamine, antibody-antigen reactions, and complement activation. Severe allergic reactions occur in ~0.04% of patients receiving nonionic media, sixfold lower than with ionic media. Risk factors include a history of prior contrast reaction (fivefold increased likelihood), food and or drug allergies, and atopy (asthma and hay fever). The predictive value of specific allergies, such as those to shellfish, once thought important, actually is now recognized to be unreliable. Nonetheless, in patients with a history worrisome for potential allergic reaction, a noncontrast CT or MRI procedure should be considered as an alternative to contrast administration. If iodinated contrast is absolutely required, a nonionic agent should be used in conjunction with pretreatment with glucocorticoids and antihistamines (Table 416-2); however, pretreatment does not guarantee safety. Patients with allergic reactions to iodinated contrast material do not usually react to gadolinium-based MR contrast material, although such reactions can occur. It would be wise to pretreat patients with a prior allergic history to MR contrast administration in a similar fashion. Subacute (>1 h after injection) reactions are frequent and probably related to T cell–mediated immune reactions. These are typically urticarial but can occasionally be more severe. Drug provocation and skin testing may be required to determine the culprit agent involved as well as determine a safe alternative.

Other side effects of CT scanning are rare but include a sensation of warmth throughout the body and a metallic taste during intravenous administration of iodinated contrast media. Extravasation of contrast media, although rare, can be painful and lead to compartment syndrome. When this occurs, consultation with plastic surgery is indicated. Patients with significant cardiac disease may be at increased risk for contrast reactions, and in these patients, limits to the volume and osmolality of the contrast media should be considered. Patients who may undergo systemic radioactive iodine therapy for thyroid disease or cancer should not receive iodinated contrast media if possible, because this will decrease the uptake of the radioisotope into the tumor or thyroid (see the American College of Radiology Manual on Contrast Media, Version 10.3, 2017; https://www.acr.org/-/media/ACR/Files/Clinical-Resources/ContrastMedia.pdf.)

TECHNIQUE

MRI is a complex interaction between hydrogen protons in biologic tissues, a static magnetic field (the magnet), and energy in the form of radiofrequency (Rf) waves of a specific frequency introduced by coils placed next to the body part of interest. Images are made by computerized processing of resonance information received from protons in the body. Field strength of the magnet is directly related to signal-to-noise ratio. While 1.5 Tesla (T) and 3-T magnets are now widely available and have distinct advantages in the brain and musculoskeletal systems, even igher field magnets (7-T) and positron emission tomography (PET) MR machines promise increased resolution and anatomic-functional information on a variety of disorders. Spatial localization is achieved by magnetic gradients surrounding the main magnet, which impart slight changes in magnetic field throughout the imaging volume. Rf pulses transiently excite the energy state of the hydrogen protons in the body. Rf is administered at a frequency specific for the field strength of the magnet. The subsequent return to equilibrium energy state (relaxation) of the hydrogen protons results in a release of Rf energy (the echo), which is detected by the coils that delivered the Rf pulses. Fourier analysis is used to transform the echo into the information used to form an MR image. The MR image thus consists of a map of the distribution of hydrogen protons, with signal intensity imparted by both density of hydrogen protons and differences in the relaxation times (see below) of hydrogen protons on different molecules. Although clinical MRI currently makes use of the ubiquitous hydrogen proton, research into sodium and carbon imaging and spectroscopy appears promising.

T1 and T2 Relaxation Times

The rate of return to equilibrium of perturbed protons is called the relaxation rate. The relaxation rate varies among normal and pathologic tissues. The relaxation rate of a hydrogen proton in a tissue is influenced by local interactions with surrounding molecules and atomic neighbors. Two relaxation rates, T1 and T2, influence the signal intensity of the image. The T1 relaxation time is the time, measured in milliseconds, for 63% of the hydrogen protons to return to their normal equilibrium state, whereas the T2 relaxation is the time for 63% of the protons to become dephased owing to interactions among nearby protons. The intensity and image contrast of the signal within various tissues can be modulated by altering acquisition parameters such as the interval between Rf pulses (TR) and the time between the Rf pulse and the signal reception (TE). T1-weighted (T1W) images are produced by keeping the TR and TE relatively short, whereas using longer TR and TE times produces T2-weighted (T2W) images. Fat and subacute hemorrhage have relatively shorter T1 relaxation rates and thus higher signal intensity than brain on T1W images. Structures containing more water, such as CSF and edema, have long T1 and T2 relaxation rates, resulting in relatively lower signal intensity on T1W images and higher signal intensity on T2W images (Table 416-3). Gray matter contains 10–15% more water than white matter, which accounts for much of the intrinsic contrast between the two on MRI (Fig. 416-4A). T2W images are more sensitive than T1W images to edema, demyelination, infarction, and chronic hemorrhage, whereas T1W imaging is more sensitive to subacute hemorrhage and fat-containing structures.

Many different MR pulse sequences exist, and each can be obtained in various planes (Figs. 416-2, 416-3, and 416-4). The selection of a proper protocol that will best answer a clinical question depends on an accurate clinical history and indication for the examination. Fluid-attenuated inversion recovery (FLAIR) is a very useful pulse sequence that produces T2W images in which the normally high signal intensity of CSF is suppressed (Fig. 416-4B). FLAIR images are more sensitive than standard spin echo images for water-containing lesions or edema, especially those close to CSF filled cisterns and sulci. Diffusion weighted imaging is also routinely obtained in most brain protocols. This sequence interrogates the microscopic motion of water, which is restricted in areas of infarction, abscess, and some tumors. SWI is very sensitive to alterations in local magnetic field generated by blood, calcium, and air. SWI is routinely obtained and helps detects microhemorrhages, such as is typical of amyloid, hemorrhagic metastases, traumatic brain injury, and thrombotic states (Fig. 416-5C). MR images can be generated in any plane without changing the patient’s position. Each sequence, however, must be obtained separately and takes 1–10 min on average to complete. Three-dimensional volumetric imaging is also possible with MRI, resulting in a three-dimensional volume of data that can be reformatted in any orientation to highlight certain disease processes.

MR Contrast Material

The heavy-metal element gadolinium forms the basis of all currently approved intravenous MR contrast agents. Gadolinium is a paramagnetic substance that reduces the T1 and T2 relaxation times of nearby water protons, resulting in a high signal on T1W images and a low signal on T2W images (the latter requires a sufficient local concentration, usually in the form of an intravenous bolus). Unlike iodinated contrast agents, the effect of MR contrast agents depends on the presence of local hydrogen protons on which it must act to achieve the desired effect. There are nine different gadolinium agents approved in the United States for use with MRI. These differ according to the attached chelated moiety, which also affects the strength of chelation of the otherwise toxic gadolinium element. The chelating carrier molecule for gadolinium can be classified by whether it is macrocyclic or has linear geometry and whether it is ionic or nonionic. Macrocyclic ligands (Group 2 agents) are considered more stable as the gadolinium ion is “caged” in the cavity of the ligand, and thus the rate of dissociation of gadolinium is slower compared to linear ligands (Group 1 agents). Most agents are excreted by the renal system.

BRAIN ACCUMULATION OF GADOLINIUM

It recently has become evident that gadolinium accumulates in the dentate nuclei and globus pallidus of the brain after serial administration of some linear Group 1 gadolinium agents. This has not been demonstrated for Group 2 macrocyclic agents. To date there is no clinical effect of this deposition that has been detected.

ALLERGIC HYPERSENSITIVITY

Gadolinium-DTPA (diethylenetriaminepentaacetic acid) does not normally cross the intact BBB immediately but will enhance lesions lacking a BBB (Fig. 416-3A) as well as areas of the brain that normally are devoid of the BBB (pituitary, dura, choroid plexus). However, gadolinium contrast slowly crosses an intact BBB over time and especially in the setting of reduced renal clearance or inflamed meninges. The agents are generally well tolerated; overall adverse events after injection range from 0.07 to 2.4%. True allergic reactions are rare (0.004–0.7%) but have been reported. Severe life-threatening reactions are exceedingly rare; in one report, only 55 reactions out of 20 million doses occurred. However, the adverse reaction rate in patients with a prior history of reaction to gadolinium is eight times higher than normal. Other risk factors include atopy or asthma (3.7%). There is no cross reactivity between different classes of contrast media; a prior reaction to gadolinium-based contrast does not predict a future reaction to iodinated contrast medium, or vice versa, more than any other unrelated allergy. Gadolinium contrast material can be administered safely to children as well as adults, although these agents are generally avoided in those aged <6 months.

NEPHROTOXICITY

Contrast-induced renal failure does not occur with gadolinium agents. A rare complication, nephrogenic systemic fibrosis (NSF), has occurred in patients with severe renal insufficiency who have been exposed to linear (Group 1 and 3) gadolinium contrast agents. The onset of NSF has been reported between 5 and 75 days following exposure; histologic features include thickened collagen bundles with surrounding clefts, mucin deposition, and increased numbers of fibrocytes and elastic fibers in skin. In addition to dermatologic symptoms, other manifestations include widespread fibrosis of the skeletal muscle, bone, lungs, pleura, pericardium, myocardium, kidney, muscle, bone, testes, and dura. The American College of Radiology recommends that a glomerular filtration rate (GFR) assessment be obtained within 6 weeks prior to elective gadolinium-based MR contrast agent administration in patients with:

1. A history of renal disease (including solitary kidney, renal transplant, renal tumor)

2. Age >60 years

3. History of hypertension

4. History of diabetes

5. History of severe hepatic disease, liver transplant, or pending liver transplant; for these patients, it is recommended that the patient’s GFR assessment be nearly contemporaneous with the MR examination.

The incidence of NSF in patients with severe renal dysfunction (GFR <30) varies from 0.19 to 4%. Other risk factors for NSF include acute kidney injury, the use of non-macrocyclic agents, and repeated or high-dose exposure to gadolinium. The American College of Radiology Committee on Drugs and Contrast Media considers the risk of NSF among patients exposed to standard or lower doses of Group 2 gadolinium agents (macrocyclic agents) is sufficiently low or possibly non-existent that the assessment of renal function is optimal prior to administration. However, patients receiving any Group 1 (linear) or 3 gadolinium-containing agent should be considered at risk of NSF if they are on dialysis (of any form); have severe or end-stage chronic renal disease (eGFR <30 mL/min/1.73 m²) without dialysis; eGFR of 30–40 mL/min/1.73 m² without dialysis (as the GFR may fluctuate); or have acute renal insufficiency. The use of gadolinium in young children and infants is discouraged due to the unknown risks and their immature renal systems.

COMPLICATIONS AND CONTRAINDICATIONS

From the patient’s perspective, an MRI examination can be intimidating, and a higher level of cooperation is required than with CT. The patient lies on a table that is moved into a long, narrow gap within the magnet. Approximately 5% of the population experiences severe claustrophobia in the MR environment. This can be reduced by mild sedation but remains a problem for some. Because it takes between 3 and 10 min per sequence, movement of the patient during an MR examination distorts all of the images; therefore, uncooperative patients should either be sedated for the MR study or scanned with CT. Generally, children aged <8 years usually require conscious sedation in order to complete the MR examination without motion degradation.

MRI is considered safe for patients, even at very high field strengths. Serious injuries have been caused, however, by attraction of ferromagnetic objects into the magnet, which act as missiles if brought too close to the magnet. Likewise, ferromagnetic implants, such as aneurysm clips, may torque within the magnet, causing damage to vessels and even death. Metallic foreign bodies in the eye have moved and caused intraocular hemorrhage; screening for ocular metallic fragments is indicated in those with a history of metal work or ocular metallic foreign bodies. Implanted cardiac pacemakers are generally a contraindication to MRI owing to the risk of induced arrhythmias; however, some newer pacemakers have been shown to be safe. All health care personnel and patients must be screened and educated thoroughly to prevent such disasters because the magnet is always “on.” Table 416-4 lists common contraindications for MRI.

MR angiography is a general term describing several MR techniques that result in vascular-weighted images. Non contrast MRA provides a flow map rather than the anatomic map shown by conventional angiography. On routine spin echo MR sequences, moving protons (e.g., flowing blood, CSF) exhibit complex MR signals that range from high- to low-signal intensity relative to background stationary tissue. Fast-flowing blood returns no signal (flow void) on routine T1W or T2W spin echo MR images. Slower-flowing blood, as occurs in veins or distal to arterial stenosis, may appear high in signal. However, using special pulse sequences called gradient echo sequences, it is possible to increase the signal intensity of moving protons in contrast to the low signal background intensity of stationary tissue. This creates angiography-like images, which can be manipulated in three dimensions to highlight vascular anatomy and relationships.

So-called time-of-flight (TOF) MRA relies on the suppression of nonmoving tissue to provide a low-intensity background for the high signal intensity of flowing blood entering the section; arterial or venous structures may be highlighted. A typical TOF MRA sequence results in a series of contiguous, thin MR sections (0.6–0.9 mm thick), which can be viewed as a stack and manipulated to create an angiographic image data set that can be reformatted and viewed in various planes and angles, much like that seen with conventional angiography (Fig. 416-2G).

Phase-contrast MRA has a longer acquisition time than TOF MRA, but in addition to providing anatomic information similar to that of TOF imaging, it can be used to reveal the velocity and direction of blood flow in a given vessel.

MRA is often acquired during infusion of contrast material. Advantages include faster imaging times (1–2 min vs 10 min), fewer flow-related artifacts, and 4D temporal imaging resulting in arterial and venous phases. Recently, contrast-enhanced MRA has become the standard for extracranial vascular MRA. This technique entails rapid imaging using coronal three-dimensional TOF sequences during a bolus infusion of gadolinium contrast agent.

MRA has lower spatial resolution compared with conventional film-based angiography, and therefore the detection of small-vessel abnormalities, such as vasculitis and distal vasospasm, is problematic. MRA is also less sensitive to slowly flowing blood and thus may not reliably differentiate complete from near-complete occlusions. Motion, either by the patient or by anatomic structures, may distort the MRA images, creating artifacts. These limitations notwithstanding, MRA has proved useful in evaluation of the extracranial carotid and vertebral circulation as well as of larger-caliber intracranial arteries and dural sinuses. It has also proved useful in the noninvasive detection of intracranial aneurysms and vascular malformations.

Recent improvements in gradients, software, and high-speed computer processors now permit extremely rapid MRI of the brain. With echo-planar MRI (EPI), fast gradients are switched on and off at high speeds to create the information used to form an image. With EPI, all of the information required for processing an image is accumulated in milliseconds, and the information for the entire brain can be obtained in <1–2 min, depending on the degree of resolution required or desired. Fast MRI reduces patient and organ motion and is the basis of perfusion imaging during contrast infusion and kinematic motion studies. EPI is also the sequence used to obtain diffusion imaging and tractography, as well as fMRI and arterial spin-labeled studies (Figs. 416-2H, 416-3, 416-4C, and 416-6; and Fig. 419-13).

Perfusion and diffusion imaging are EPI techniques that are useful in early detection of ischemic injury of the brain and may be useful together to demonstrate infarcted tissue as well as ischemic but potentially viable tissue at risk of infarction (e.g., the ischemic penumbra). Diffusion-weighted imaging (DWI) assesses microscopic motion of water; abnormal restriction of motion appears as relative high-signal intensity on diffusion-weighted images. Infarcted tissue reduces the water motion within cells and in the interstitial tissues, resulting in high signal on DWI. DWI is the most sensitive technique for detection of acute cerebral infarction of <7 days in duration (Fig. 416-2H). It is also quite sensitive for detecting dying or dead brain tissue secondary to encephalitis, as well as abscess formation (Fig. 416-3B).

Perfusion MRI can be performed by the acquisition of fast echo planar gradient images during a rapid intravenous bolus of gadolinium contrast material or by arterial spin labeling (ASL) without the use of contrast material. With contrast perfusion imaging, relative cerebral blood volume, mean transit time, and cerebral blood flow maps are derived. Delay in mean transit time and reduction in cerebral blood volume and cerebral blood flow are typical of infarction. In the setting of reduced blood flow, a prolonged mean transit time of contrast but normal or elevated cerebral blood volume may indicate tissue supplied by collateral flow that is at risk of infarction. Perfusion MRI imaging can also be used in the assessment of brain tumors to differentiate intraaxial primary tumors, whose BBB is relatively intact, from extraaxial tumors or metastases, which demonstrate a relatively more permeable BBB.

Diffusion tensor imaging is derived from diffusion MRI imaging sequences. This technique assesses the direction and integrity of white matter architecture. It has proven valuable in preoperative assessment of subcortical white matter tract anatomy prior to brain tumor surgery, as well as determining normal and abnormal white matter architecture in congenital and acquired pathologies (Fig. 416-6).

fMRI of the brain is an EPI technique that localizes regions of activity in the brain following task activation or at rest (so-called resting state fMRI). Neuronal activity elicits a slight increase in the delivery of oxygenated blood flow to a specific region of activated brain. This results in an alteration in the balance of oxyhemoglobin and deoxyhemoglobin, which yields a 2–3% increase in signal intensity within veins and local capillaries. Currently, preoperative somatosensory and auditory cortex localization is possible, and methods to assess motor and language function are in development. This technique has proved useful to neuroscientists interested in interrogating the localization of certain brain functions.

ASL is a quantitative noninvasive MR technique that measures cerebral blood flow. Blood traversing in the neck is labeled by an MR pulse and then imaged in the brain after a short (2 second) delay. The signal in the brain is reflective of blood flow. ASL is an especially important technique for patients with kidney failure and for pediatric patients in whom the use of radioactive tracers or exogenous contrast agents is contraindicated. Increased cerebral flow is more easily identified than slow flow, which can be sometimes difficult to quantify. This technique has also been useful in detecting arterial venous shunting in arteriovenous malformations and arteriovenous fistulas, as well as increased blood flow in brain tumors, and patients post TIA, post-ictal, or post migrane.

MRN is a T2W MR technique that shows promise in detecting increased signal in irritated, inflamed, or infiltrated peripheral nerves. Images are obtained with fat-suppressed fast spin echo imaging or short inversion recovery sequences. Irritated or infiltrated nerves will demonstrate high signal on T2W imaging. This is indicated in patients with radiculopathy whose conventional MR studies of the spine are normal, or in those suspected of peripheral nerve entrapment or trauma.

PET relies on the detection of positrons emitted during the decay of a radionuclide that has been injected into a patient. The most frequently used moiety is 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG), which is an analogue of glucose and is taken up by cells competitively with 2-deoxyglucose. Multiple images of glucose uptake activity are formed after 45–60 min. Images reveal differences in regional glucose activity among normal and pathologic brain structures. FDG-PET is used primarily for the detection of extracranial metastatic disease; however, a lower activity of FDG in the parietal lobes is associated with Alzheimer’s disease, a finding that may simply reflect atrophy that occurs in the later stages of the disease. Combination PET-CT scanners, in which both CT and PET are obtained at one sitting, have largely replaced PET scans alone for most clinical indications. MR-PET scanners have also been developed and may prove useful for imaging the brain and other organs without the radiation exposure of CT. More recent PET ligand developments include beta-amyloid tracers, such as Pittsburgh compound B (PIB) and 18-F AV-45 (florbetapir), and tau PET tracers, such as 18F-T807 and T808. Studies have shown an increased percentage of amyloid deposition in patients with Alzheimer’s disease compared with mild cognitive impairment and healthy controls; however, up to 25% of cognitively “normal” patients show abnormalities on amyloid PET imaging. This may either reflect subclinical disease processes or variation of normal. Tau imaging may be more specific for Alzheimer’s disease, and clinical studies are under way.

TECHNIQUE

Myelography involves the intrathecal instillation of specially formulated water-soluble iodinated contrast medium into the lumbar or cervical subarachnoid space. CT scanning is typically performed after myelography (CT myelography) to better demonstrate the spinal cord and roots, which appear as filling defects in the opacified subarachnoid space. Low-dose CT myelography, in which CT is performed after the subarachnoid injection of a small amount of relatively dilute contrast material, has replaced conventional myelography for many indications, thereby reducing exposure to radiation and contrast media. CT is obtained at a slice thickness ~ 2.5 mm and reconstructed at 0.625-mm thick slices which can quickly be reformated in sagittal and coronal planes, equivalent to traditional myelography projections.

INDICATIONS

CT myelography and MRI have largely replaced conventional myelography for the diagnosis of diseases of the spinal canal and cord (Table 416-1). Remaining indications for conventional plain-film myelography include the evaluation of suspected meningeal or arachnoid cysts and the localization of CSF fistulas. Conventional myelography and CT myelography provide the most precise information in patients with failed back syndrome following spinal fusion procedures.

CONTRAINDICATIONS

Myelography is relatively safe; however, it should be performed with caution in any patient with elevated intracranial pressure, evidence of a spinal block, or a history of allergic reaction to intrathecal contrast media. In patients with a suspected spinal block, MR is the preferred imaging technique. If myelography is necessary, only a small amount of contrast medium should be instilled below the block in order to minimize the risk of neurologic deterioration. Lumbar puncture is to be avoided in patients with bleeding disorders, including patients receiving anticoagulant therapy, as well as in those with infections of the overlying soft tissues.

COMPLICATIONS

Headache is the most frequent complication of myelography and is reported to occur in 5–30% of patients. Nausea and vomiting may also occur rarely. Postural headache (post–lumbar puncture headache) is generally due to continued leakage of CSF from the dural puncture site. A higher incidence is noted among younger women and with the use of larger gauge cutting-type spinal needles. If significant headache persists for >48 h, placement of an epidural blood patch should be considered. Management of lumbar puncture headache is discussed in Chap. 13. Vasovagal syncope may occur during lumbar puncture; it is accentuated by the upright position used during lumbar myelography. Adequate hydration before and after myelography will reduce the incidence of this complication.

Hearing loss is a rare complication of myelography. It may result from a direct toxic effect of the contrast medium or from an alteration of the pressure equilibrium between CSF and perilymph in the inner ear. Puncture of the spinal cord is a rare but serious complication of cervical (C1–2) or high lumbar puncture. The risk of cord puncture is greatest in patients with spinal stenosis, Chiari malformations, or conditions that reduce CSF volume. In these settings, a low-dose lumbar injection followed by thin-section CT or MRI is a safer alternative to cervical puncture. Intrathecal contrast reactions are rare, but aseptic meningitis and encephalopathy are reported complications. The latter is usually dose related and associated with contrast entering the intracranial subarachnoid space. Seizures rarely occur following myelography, historically reported in 0.1–0.3% of patients. Risk factors include a preexisting seizure disorder and the use of a total iodine dose of >4500 mg. Other reported complications include hyperthermia, hallucinations, depression, and anxiety states. These side effects have been reduced by the development of nonionic, water-soluble contrast agents as well as by head elevation and generous hydration following myelography.

DISKOGRAPHY

The evaluation of back pain and radiculopathy may require diagnostic procedures that attempt either to reproduce the patient’s pain or relieve it, indicating its correct source prior to lumbar fusion. Diskography is performed by fluoroscopic placement of a 22- to 25-gauge needle into the intervertebral disk and subsequent injection of 1–3 mL of contrast media. The intradiskal pressure is recorded, as is an assessment of the patient’s response to the injection of contrast material. Typically little or no pain is felt during injection of a normal disk, which does not accept much more than 1 mL of contrast material, even at pressures as high as 415–690 kPa (60–100 lb/in²). CT and plain films are obtained following the procedure. Concerns have been raised that diskography may contribute to an accelerated rate of disk degeneration; furthermore, patients who suffer from depression or anxiety are more likely to find diskography painful and in some cases the procedure-associated pain became persistent, lasting a year or longer.

SELECTIVE NERVE ROOT AND EPIDURAL SPINAL INJECTIONS

Percutaneous selective nerve root and epidural blocks with glucocorticoid and anesthetic mixtures may be both therapeutic and diagnostic, especially if a patient’s pain is relieved. Typically, 1–2 mL of an equal mixture of a long-acting glucocorticoid such as betamethasone and a long-acting anesthetic such as bupivacaine 0.75% is instilled under CT or fluoroscopic guidance in the intraspinal epidural space or adjacent to an existing nerve root. This can also be performed in the facet joints, or around the medial nerve branches that supply innervation to the facet joints.

Catheter angiography is indicated for evaluating intracranial small-vessel pathology (such as vasculitis), for assessing vascular malformations and aneurysms, and in endovascular therapeutic procedures (Table 416-1). As noted above, angiography has been replaced for many indications by CT/CTA or MRI/MRA.

Angiography carries the greatest risk of morbidity of all diagnostic imaging procedures, owing to the necessity of inserting a catheter into a blood vessel, directing the catheter to the required location, injecting contrast material to visualize the vessel, and removing the catheter while maintaining hemostasis. Therapeutic transcatheter procedures (see below) have become important options for the treatment of some cerebrovascular diseases. The decision to undertake a diagnostic or therapeutic angiographic procedure requires careful assessment of the goals of the investigation and its attendant risks.

To improve tolerance to contrast agents, patients undergoing angiography should be well hydrated before and after the procedure. Because the femoral route is used most commonly, the femoral artery must be compressed after the procedure to prevent a hematoma from developing. The puncture site and distal pulses should be evaluated carefully after the procedure; complications can include thigh hematoma or lower extremity emboli.

COMPLICATIONS

A common femoral arterial puncture provides retrograde access via the aorta to the aortic arch and great vessels. The most feared complication of cerebral angiography is stroke. Thrombus can form on or inside the tip of the catheter, and atherosclerotic thrombus or plaque can be dislodged by the catheter or guide wire or by the force of injection and can embolize distally in the cerebral circulation. Risk factors for ischemic complications include limited experience on the part of the angiographer, atherosclerosis, vasospasm, low cardiac output, decreased oxygen-carrying capacity, advanced age, and prior history of migraine. The risk of a neurologic complication varies but is ~4% for transient ischemic attack and stroke, 1% for permanent deficit, and <0.1% for death.

Ionic contrast material injected into the cerebral vasculature can be neurotoxic if the BBB is breached, either by an underlying disease or by the injection of hyperosmolar contrast agent. Ionic contrast media are less well tolerated than nonionic media, probably because they can induce changes in cell membrane electrical potentials. Patients with dolichoectasia of the basilar artery can suffer reversible brainstem dysfunction and acute short-term memory loss during angiography, owing to the slow percolation of the contrast material and the consequent prolonged exposure of the brain. Rarely, an intracranial aneurysm ruptures during an angiographic contrast injection, causing subarachnoid hemorrhage, perhaps as a result of injection under high pressure.

SPINAL ANGIOGRAPHY

Spinal angiography may be indicated to evaluate vascular malformations and tumors and to identify the artery of Adamkiewicz (Chap. 434) prior to aortic aneurysm repair. The procedure is lengthy and requires the use of relatively large volumes of contrast; the incidence of serious complications, including paraparesis, subjective visual blurring, and altered speech, is ~2%. Gadolinium-enhanced MRA has been used successfully in this setting, as has iodinated contrast CTA, which has promise for replacing diagnostic spinal angiography for some indications.

This rapidly developing field is providing new therapeutic options for patients with challenging neurovascular problems. Available procedures include detachable coil therapy for aneurysms, particulate or liquid adhesive embolization of arteriovenous malformations, stent retrieval systems for embolectomy, balloon angioplasty and stenting of arterial stenosis or vasospasm, transarterial or transvenous embolization of dural arteriovenous fistulas, balloon occlusion of carotid-cavernous and vertebral fistulas, endovascular treatment of vein-of-Galen malformations, preoperative embolization of tumors, and thrombolysis of acute arterial or venous thrombosis. Many of these disorders place the patient at high risk of cerebral hemorrhage, stroke, or death.

The highest complication rates are found with the therapies designed to treat the highest risk diseases. The advent of electrolytically detachable coils ushered in a new era in the treatment of cerebral aneurysms. Two randomized trials found reductions of morbidity and mortality at 1 year among those treated for aneurysm with detachable coils compared with neurosurgical clipping. It remains to be determined what the role of coils will be relative to surgical options, but in many centers, coiling has become standard therapy for many aneurysms.

Finally, recent studies of stent retrieval systems used to withdraw emboli have shown improved clinical outcomes in patients presenting with large vessel occlusions and signs of stroke (Chap. 420).