Principles of Modern Neuroimaging


Clinical Pearls

  • Noncontrast head computed tomography (CT) is the imaging test of choice in the evaluation of acute neurologic disease such as head trauma, hemorrhage, and acute hydrocephalus.

  • Noncontrast head CT can also detect early signs of ischemic stroke, including sulcal effacement, loss of gray-white matter differentiation, and dense vessel signs.

  • In CT perfusion of acute stroke, areas of ischemic penumbra show prolonged mean transit times and normal cerebral blood volume. These areas are potentially salvageable with neurointerventional therapies.

  • Intravenous contrast is useful in the detailed evaluation of vascular structures, as well as for the identification of blood-brain barrier breakdown, such as occurs with mass lesions and infection.

  • Vascular flow voids are best seen on T2-weighted magnetic resonance imaging (MRI), and edema is best assessed with fluid attenuated inversion recovery imaging.

  • T2*-weighted gradient echo and susceptibility-weighted sequences highlight blood degradation products in assessment of subtle hemorrhages or small cavernous malformations.

  • Functional MRI detects changes in blood oxygenation within areas of the brain involved in specific tasks such as language, vision, or movement.

  • Areas of restricted diffusion (such as acute stroke) appear bright on diffusion-weighted imaging (DWI) sequences and dark on apparent diffusion coefficient (ADC) maps. These sequences also help characterize ring-enhancing lesions; primary CNS lymphoma and the central nonenhancing areas of pyogenic abscesses are typically bright on DWI and dark on ADC maps, whereas the necrotic regions of gliomas and metastases are not.

  • Diffusion tensor imaging measures organized fluid movement along white matter tracts and can help guide safe resection of lesions in eloquent locations.

  • Seizure foci show ictal hyperperfusion and interictal hypoperfusion in single-photon emission CT imaging.

Neuroimaging is vital to the practice of neurosurgery, and an understanding of the strengths and limitations of different imaging modalities is important for the practicing neurosurgeon. As the number of imaging studies performed worldwide has increased, issues of patient safety, including the risks of ionizing radiation and contrast use, and rising health care costs have become increasingly important.

Even though the number of randomized controlled studies and cost-effectiveness analyses regarding the use of imaging in neurosurgical practice remains small, this is changing. In an effort to provide clinicians with easy access to current data on the most effective imaging modalities for a particular clinical question, the American College of Radiology (ACR) has established criteria to evaluate the use of imaging in patient care, called the ACR Appropriateness Criteria. These criteria are composed by consensus among a panel of experts in radiology with input from nonradiology experts based on critical reviews of the literature. The criteria are available online through a searchable database organized by patient symptoms and imaging modality using a free search engine ( https://acsearch.acrorg/list ).

This chapter describes the fundamentals of currently used imaging techniques and highlights the advantages of different techniques in evaluating neurosurgical illness. Important considerations of radiation exposure and risks of contrast agents are discussed briefly. Next, the key general imaging findings pertinent to neurosurgeons are surveyed in detail in the sections on computed tomography (CT). The section on magnetic resonance imaging (MRI) approaches the topic from a different angle, highlighting advantages of specific imaging sequences. Angiographic modalities of CT and MRI are then addressed. Advanced imaging techniques including diffusion tensor imaging (DTI), spectroscopy, and functional MRI are also briefly discussed.

Principles

Radiography

Discovered by Wilhelm Roentgen in 1895, x-rays are photons carrying electromagnetic energy that are created by an anode-cathode system within a vacuum. X-ray photons are of higher energy and shorter wavelength than visible light. When x-ray photons collide with atoms of varying sizes, they either pass through or are absorbed. Larger (heavier, radiopaque) atoms, such as calcium or metals, are more likely to absorb the energy of the photons than smaller (lighter, radiolucent) atoms and small molecules, such as water or air. When a patient is positioned in a beam of x-rays, the x-rays will be differentially absorbed based on the tissue components (bone, soft tissue, aerated sinuses). Photons that pass through the patient strike a detector and create an x-ray image, producing a two-dimensional projected image of the different attenuation properties of body tissue.

Fluoroscopy is a variation of radiography in which images are obtained in rapid succession and displayed in real time on a screen. In angiography, intravenous contrast material is injected into vessels during continuous fluoroscopy. Digital subtraction angiography (DSA) is a technique in which a baseline or mask image is initially obtained of the area of interest. This baseline image is subtracted from subsequent images obtained during intravascular contrast injection, optimizing visualization of the contrast agent itself within opacified vessels. With modern angiography systems, images can be acquired from multiple different projections during a single contrast injection by rapidly rotating the fluoroscopy unit around the patient, allowing reconstruction of a three-dimensional image of the vascular structures.

Computed Tomography

Sir Godfrey Hounsfield and Dr. Allan Cormack invented the first computed axial tomographic scanner in 1972, which earned them the Nobel Prize for medicine in 1979. CT scanners have advanced significantly since that time, rapidly increasing in speed and resolution. Modern scanners use a rotating x-ray tube and detector array that revolve around the body, obtaining tissue attenuation information from beams or rays of tissues within a slab. Standard axial images are obtained by applying a reconstruction algorithm, typically filtered back projection, to reconstruct the two-dimensional image. Sagittal, coronal, or oblique imaging planes can be reconstructed from the axial sequences by computer reformatting. Radiodense contrast material administered intravenously or parenterally can outline hollow structures such as blood vessels or the digestive system.

CT density is quantitatively measured in Hounsfield units (HU). Hounsfield units describe a linear scale of attenuation that is constant across scanner platforms, with water and air given arbitrary values of 0 and −1000, respectively. Materials with increased x-ray attenuation with respect to water have a positive HU value, and those with less x-ray attenuation than water have a negative HU value ( Table 4.1 ).

TABLE 4.1
Computed Tomography Hounsfield Unit Values
Tissue Hounsfield Units
Air −1000
Fat −(60–100)
Water 0
White matter 35
Gray matter 45
Blood—acute hemorrhage 50–70
Calcium >150
Dense bone 1000
Metal ≫1000

CT images can be viewed in different ways to accentuate different tissues. Window level describes the center point of the gray scale, and window width describes the range of CT values displayed. For example, gray matter has an attenuation of approximately 35 HU, and white matter attenuation is approximately 45 HU. To differentiate gray matter from white matter, a narrow window is needed to highlight small changes in HU values. On the other hand, if detailed evaluation of dense material such as bone is desired, a wide window better delineates the radiodense edges. Window level and width are easily manipulated using most imaging viewing software.

In addition to window width and level, CT scans are generally processed using different reconstruction filters, frequently referred to as bone and standard algorithms . Both filters can be applied to a single acquisition of data, allowing accentuation of different structures. Standard algorithm is a method of averaging adjacent pixels to accentuate soft tissue detail. Standard algorithm images are useful for evaluating gray-white matter differentiation and for detecting acute blood. Bone algorithm images are processed to maximize edges, thus accentuating high-density materials such as calcium and metal. Bone algorithm images are also useful for evaluating lung parenchyma due to the differences in attenuation between aerated lung and small soft tissue attenuation structures such as blood vessels and pulmonary nodules.

Issues With Computed Tomography

Radiation Exposure.

There is increasing awareness among health care providers and the general public of radiation exposure from medical imaging and the carcinogenic potential of x-rays. This is in part related to the dramatic increase in the utilization of CT. According to the American College of Radiology White Paper on Radiation Dose in Medicine, approximately 3 million CT studies were performed in 1980, compared to approximately 60 million in 2005. Although CT has undoubtedly contributed positively to the care of patients, the cumulative radiation dose may have increased the risk of cancer in exposed patients, and up to 1% of U.S. cancers may be related to medical exposures. Based on studies of Japanese atomic bomb survivors, cancer risk increases with exposures as low as 50 mSv (millisieverts). A millisievert is a measure of effective radiation dose, which is weighted for tissue sensitivity to the negative effects of radiation.

Cancer risk depends on tissue type, and neural tissue is relatively resistant. Exposure to more radiosensitive tissues may also occur with neuroimaging. For example, exposure of the cornea may lead to cataracts in a dose-dependent fashion. The lens of the eye receives a dose of up to 50 mGy (milligray, a measure of absorbed dose) per head CT, which can potentially be reduced by eye shielding or dose reduction features available on modern CT scanners. Lens opacities have been seen with as little exposure as 500 mGy (10 CT scan equivalents), with vision-limiting cataracts forming at doses greater than 4 Gy (approximately 80 CT scan equivalents). In 2011 the International Commission on Radiological Protection issued a Statement on Tissue Reactions that lowered the absorbed dose threshold to 500 mGy for the lens of the eye. Children are more susceptible than adults.

The “as low as reasonably achievable” (ALARA) principle of keeping exposure to a minimum is an important guideline to follow when imaging patients, particularly when ionizing radiation will be used. This principle aims to balance the clinical benefit of the imaging study with the risks, however low they may be. Additionally, physicians should take care to protect themselves when using fluoroscopy for angiography and during implant and spine procedures. Specific questions about radiation exposure and protection can be addressed to the local staff radiologist or medical physicist.

Iodinated Contrast Agents.

Iodinated contrast material may be associated with contrast-induced nephropathy (CIN) in patients with renal failure, particularly those with diabetes mellitus. CIN refers to a sudden deterioration in renal function, most commonly defined as an absolute increase of 0.5 mg/dL over a baseline serum creatinine, due to the intravascular administration of iodinated contrast. Strategies to reduce the risk of CIN include volume expansion through intravenous or oral fluids. Sodium bicarbonate infusion and prophylactic N -acetylcysteine have also shown efficacy compared to normal saline infusion. In patients with diminished renal function, reduced doses of contrast agent or iso-osmolar nonionic contrast agent can be considered. Of course, the best prevention of CIN is the avoidance of intravenous contrast material altogether, although this is not always feasible.

Another potential complication of iodinated contrast agent is allergic contrast reaction. The incidence of contrast reaction after a CT contrast scan is 0.2% to 0.7% (approximately 1/225). Contrast reactions may be mild or severe. Most reactions are mild, including nausea, vomiting, or rash. Severe reactions occur infrequently, with an incidence of approximately 0.05% (1/2000) for low osmolar iodinated contrast agent. Severe allergic contrast reactions include bronchospasm, laryngeal edema, and cardiovascular collapse.

In patients with a history of moderate or severe contrast allergy, premedication strategies decrease, but do not eliminate, the risk of recurrent contrast reaction. Standard oral premedication strategies include prednisone (50 mg by mouth at 13, 7, and 1 hour prior to contrast injection) or methylprednisolone (32 mg by mouth at 12 and 2 hours before contrast injection), along with diphenhydramine (50 mg 1 hour prior to injection). An accelerated IV premedication regimen consisting of methylprednisolone sodium succinate (40 mg IV) or hydrocortisone sodium succinate (200 mg IV) immediately and then repeated every 4 hours prior to contrast administration, plus diphenhydramine (50 mg IV) 1 hour prior to contrast administration, requires at least 4 to 5 hours duration and is less supported by evidence than standard oral regimens. Premedication regimens of less than 4 to 5 hours duration are generally considered ineffective for prevention of allergic contrast reactions.

Magnetic Resonance Imaging

Magnetic resonance imaging was developed by a host of innovative scientists over multiple decades of development from a scientific tool to a medical imaging necessity. MRI is based on the principles of nuclear magnetic resonance (NMR), first discovered by Felix Bloch and Edward Purcell, for which they were awarded the Nobel Prize in physics in 1952. NMR can be utilized to characterize and differentiate tissues based on their intrinsic NMR signal. Using NMR techniques, chemist Paul C. Lauterbur and physicist Sir Peter Mansfield developed the gradients and mathematical formulations required for rapid two-dimensional MR images, publishing the first images in 1973 and 1974. Drs. Raymond Damadian, Larry Minkoff, and Michael Goldsmith were also instrumental in the development and refining of this technology for use in humans. For their pioneering work in MRI development, Drs. Lauterbur and Mansfield shared the Nobel Prize in physiology or medicine in 2003.

The detailed physics principles underlying MRI are highly complex and beyond the scope of this chapter. In brief, a powerful electromagnetic field is created within the bore of an MRI machine, typically along the cranial-caudal (z) axis. Protons that are present in the human body predominantly as hydrogen atoms in water molecules reach equilibrium aligned along the direction of this magnetic field (longitudinal magnetization). A radiofrequency (RF) pulse is applied at a resonance frequency specific to the protons within the main magnetic field (B-zero), causing them to absorb energy and change their alignment toward the horizontal/vertical plane (x-y axes), called transverse magnetization. When the RF pulse ends, the protons first dephase in the x-y direction (free-induction decay, the basis of T2 signal) at a rate dependent on the molecular structure of the sample. The protons then realign along the z-axis (spin-lattice relaxation, the basis of T1 signal) at a slower rate, which is dependent on the molecular structure surrounding the proton. As the protons realign toward equilibrium, they emit RF energy that is detected by antennas (receiver coil) surrounding the patient in the scanner. By inducing small changes in frequency and phase of the proton resonance frequency that vary as a function of proton position, the MRI system reconstructs the precise location of each signal within the patient. The MRI system thus produces cross-sectional images through the patient where each pixel (corresponding to a defined volume of tissue, or voxel) depends on the magnetic microenvironment of the corresponding tissue.

From this general principle, a variety of pulse sequences have been developed to emphasize different tissue characteristics. A pulse sequence refers to a specific pattern of RF pulses that may vary in timing, order, repetition, and direction. Basic pulse sequences include spin echo, gradient echo including T2* gradient recalled echo (GRE) and susceptibility-weighted imaging (SWI), inversion recovery including short tau inversion recovery (STIR) and fluid attenuated inversion recovery (FLAIR), and echo planar imaging used in diffusion, perfusion, and functional MR techniques. The clinical applications of those sequences most pertinent to neuroradiology are described in this chapter.

MR angiography (MRA) can be performed by several techni­ques, including time-of-flight, phase-contrast, and gadolinium-enhanced MRA. In time-of-flight angiography, protons in moving blood are tagged in one tissue slab by applying an RF pulse to change their longitudinal magnetization. Tagged protons are subsequently detected in a different tissue slab that has not experienced the RF pulse. The direction of blood flow can be selected by applying a saturation pulse to null the longitudinal magnetization from protons traveling in the opposite direction. For example, to selectively visualize tagged blood protons moving superiorly within the cervical arteries, a saturation pulse is applied superior to the scan volume (eg, within the head) to neutralize the longitudinal magnetization of the tagged protons within the intracranial compartment before they travel inferiorly in the cervical veins.

Phase contrast angiography is another method to detect moving protons such as those in blood or CSF. Phase contrast imaging depends on applying bipolar gradients to protons, so that stationary protons experience both positive and negative gradients, with no net phase change. Moving protons experience only one gradient before moving out of the field, resulting in positive or negative excitation.

Contrast-enhanced angiography uses gadolinium-based contrast agents to highlight blood vessels. Gadolinium is strongly paramagnetic, resulting in significant T1 shortening (high signal on T1-weighted sequences). After intravenous administration of gadolinium, T1-weighted sequences can be obtained during the arterial or venous phase to highlight vascular anatomy. Three-dimensional reformatted sequences can be constructed after any of the angiographic techniques.

Issues With Magnetic Resonance Imaging

MRI offers many advantages over CT. MRI provides excellent soft tissue detail and does not use ionizing radiation, but it does have several drawbacks. Study times for MRI are significantly longer than those for CT. MR images are significantly degraded by motion artifact, which coupled with the longer scan times becomes problematic in acutely ill patients and children. MRI coils must be in close approximation to the body area being imaged, and the bore of the MRI scanner is generally both smaller and more enclosed than CT. This can be a significant problem for patients with claustrophobia or those with a large body habitus.

Because of the strong magnetic fields used for MRI, it is not safe to scan patients with certain metal implants or ferromagnetic foreign bodies. Some metal implants or foreign bodies can move because of the influence of the external magnetic field, with potentially devastating consequences depending on the nature of the object (eg, older ferromagnetic aneurysm clips). Certain metallic objects can heat during scanning, which can be uncomfortable to the patient or cause tissue damage. These effects of the magnetic field are more pronounced at higher field strength magnets (that is, 3-tesla compared to 1.5-tesla scanners). In addition, certain implants, such as vagal nerve stimulators, deep brain stimulators, and cardiac pacemakers, can malfunction or cause tissue damage due to RF-induced heating during exposure to strong magnetic fields. It is worth remembering that implanted devices or other foreign bodies do not need to lie within the area of interest (scan volume) in order to be affected by the magnetic fields of the MR scanner, and that in modern scanners the main magnetic field is always present.

There are several resources available to determine whether a particular implant is compatible or considered safe to scan with MRI, including a website maintained by the Institute for Magnetic Resonance Safety, Education, and Research ( http://mrisafety.com ). This website includes a free searchable database of the safety profile of many different implants and devices. The radiologist or MRI technologist can also provide valuable advice on MR safety.

Gadolinium Contrast Agents.

Gadolinium-based contrast agents used in MRI have associated risks. The risk of allergic contrast reaction after gadolinium-based contrast agent injection is lower than for iodinated contrast, with a reported incidence of 0.04% to 0.07% (approximately 1/2000). In one large series of contrast reactions after gadolinium-based contrast agent, 88% were considered mild. The overall incidence of severe reactions (those requiring epinephrine for treatment) was 0.001% to 0.01% of injections (approximately 1/20,000).

Since 2006 an association between gadolinium-based contrast administration and nephrogenic systemic fibrosis (NSF) has been recognized in patients with renal failure. NSF is a progressive fibrosing disease affecting the skin and soft tissues, often of the extremities. NSF may also affect striated muscle and the diaphragm. There is no clearly effective treatment. This entity is believed to be associated with gadolinium deposition in tissues and is not prevented by dialysis.

NSF is rare, with an incidence of 1% to 7% in patients with renal dysfunction who receive gadolinium. It is associated with severe acute renal failure or chronic renal failure with an estimated glomerular filtration rate (GFR) of less than 15 to 30 mL/minute. It is also associated with renal or liver transplantation. Because of this association, gadolinium agents should be used with caution in patients with compromised renal function and should be avoided if possible in patients with GFR less than 30 mL/minute. Gadolinium-based contrast agents have been classified according to the strength of their association with developing NSF, and the use of certain contrast agents associated with the greatest number of NSF cases is now contraindicated by the US Food and Drug Administration (FDA) in high-risk patients. The risks of administering gadolinium-based contrast agent to a high-risk patient should be weighed against the risks of not performing a necessary contrast-enhanced imaging exam in that individual patient, and therefore discussion of such cases with the local radiologist is recommended.

Published reports of residual gadolinium deposition within brain tissue of patients who received multiple doses of gadolinium-based contrast agents over their lifetimes have emerged. Some regions of the brain, including the globi pallidi and dentate nuclei, appear to be more affected than others, and certain contrast agents are more strongly associated with this phenomenon than others. The deposition of residual gadolinium occurs in the setting of an intact blood-brain barrier and normal renal function, and the precise mechanisms whereby this occurs are unknown at this time. Although the health risks and clinical significance of residual gadolinium deposition are being actively investigated, to date no known adverse health effects have been uncovered.

Clinical Imaging

Radiography

Once the mainstay of neuroradiology, skull radiography and its permutations have been largely replaced by cross-sectional imaging modalities such as CT and MRI. Radiography is still used in the evaluation of shunts and other neurosurgical implants such as intrathecal pumps and deep brain stimulators.

Shunt series are the most commonly encountered of these studies and include radiographs of the shunt components in two planes. Shunt series are used to evaluate the nature of the shunt, including the location of the ventricular and distal catheters, drainage location (eg, atrial, peritoneal, pleural), and the type and setting of the shunt valve, as well as to identify causes of shunt dysfunction. Shunt catheters, valves, and tubing can be quickly examined for kinks or disruption, without the cost or radiation exposure of CT or the time and cost of MRI. The type and setting of most implanted shunt valves can also be determined based on radiographic appearance.

Radiography is also sometimes used in the evaluation of the bony calvarium. Although CT has largely replaced radiography for evaluation of facial fractures or sinusitis, skull films are occasionally obtained for these purposes. Linear nondisplaced skull fractures that may be missed on axial CT can at times be detected by radiography. Such occult fractures can sometimes be visualized by either examining the scout tomographic view obtained as part of a routine CT scan or by constructing surface-rendered three-dimensional (3D) reformats of CT images. In addition, skull films are sometimes obtained to evaluate for radiolucent bone lesions prior to the placement of stereotactic frames for Gamma Knife treatment or stereotactic biopsy.

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