Plain Radiographs

Though plain radiographs were used for a lot of neurodiagnostic work, especially trauma patients, the advent of multiplanar imaging techniques, mainly CT and MRI, has relegated that role to the confines of history. Skull or spine radiographs can detect fractures; however, sensitivity is less than that of CT and intracranial and intraspinal injury cannot be as accurately evaluated by plain radiographs. Besides trauma, one practical use for skull radiographs which is still used in present settings is to exclude metallic foreign body in orbits prior to MRI.

Computed Tomography

It is not wrong to say that CT is the workhorse of a modern neurodiagnostic imaging facility, especially in emergent settings. Its widespread availability and short scan time make it the preferred imaging modality for initial evaluation of many intracranial lesions. The short scan time makes it especially useful in the settings of stroke and trauma in agitated, unstable patients who can benefit tremendously from the early detection of and neurosurgical intervention in incidences such as intracranial hemorrhage, hydrocephalus, and impending herniation. The early detection prompts early surgical intervention, which has been documented as improving patient outcomes. This has resulted in the increased utilization of CT scans in emergency departments over the last decade. Another advantage is volumetric data acquisition, which helps in better evaluation of intracranial and spinal structures in three dimensions. The principal disadvantage of CT is the ionizing radiation exposure, which has prompted, among other things, a campaign among clinicians and radiologists, the “Image Gently” campaign, to popularize a means of reducing the radiation dose in pediatric settings. One of the other disadvantages of CT is its inability to assess lesions in areas such as the posterior fossa and the floor of the middle cranial fossa due to “beam hardening” artifacts resulting from the attenuation of the X-ray beam behind relatively dense structures such as the clivus and temporal bone. Contrast agents commonly used in CT are iodine-based, the majority now being nonionic, resulting in lesions being more conspicuous due to breakdown of the blood–brain barrier.

Magnetic Resonance Imaging

MRI is increasingly being used for the delineation of details of the anatomy and also of complex lesions of the central nervous system. It uses the signals emitted by the relaxation of ubiquitous hydrogen nuclei present in water after they have been excited by radiofrequency pulses in a strong magnetic field. By varying the different pulse sequences in obtaining images, the soft tissue contrast of visualized anatomical structures can be varied. On T1-weighted images, fat appears bright and water and cerebrospinal fluid (CSF) appear black. On T2-weighted images, fat has intermediate signal appearing gray, while water and CSF appear bright. Cortical bone, composed of relatively fixed protons, does not produce a signal. Flowing blood produces no signal resulting in a so-called “signal void.” In general, pathologic processes usually contain excess amounts of free water and therefore are dark on T1-weighted images and bright on T2-weighted images. Hence, the rule of thumb is that anatomy is better seen on T1-weighted and pathology better on T2-weighted sequences. Contrast agents in the majority of cases are paramagnetic (eg, gadolinium-DTPA) and result in vessels and pathologic lesions being more conspicuous due to an increased T1 signal. This is the reason that post-contrast sequences are T1-weighted.

Different pulse sequences can be used for different types of CNS lesions. One of the commonest sequences to be used in all brain MRIs is the DWI sequence, which is particularly helpful in detecting early ischemia. This we shall discuss further in the functional neuroimaging section. Fluid-attenuated inversion recovery (FLAIR) sequence increases the conspicuity of focal hyperintense T2 signal in pathologic lesions by eliminating (or “nulling”) the hyperintense CSF signal. Thus, focal bright gray matter abnormalities in contusions or white matter abnormalities in diffuse axonal injuries (DAI) or multiple sclerosis are more easily appreciated against the adjacent “nulled” dark CSF spaces. FLAIR also has increased sensitivity for the presence of acute or subacute subarachnoid hemorrhage (SAH), which appears as a hyperintense signal within the sulci and cisterns. The gradient-echo (GRE) T2*-weighted MR sequence shows increased sensitivity for detection of intracranial blood. However, susceptibility-weighted imaging (SWI) has now proven to be more sensitive and better in detecting hemorrhage and calcification.

Magnetic resonance safety protocols and extensive pre-procedural screening are needed for the safety of the patients with the increasing use of biomedical implants and devices. Cardiac pacemakers, intraocular metallic fragments, mechanical device implants such as cochlear implants, drug infusion pump, neurostimulators for deep brain stimulation, and ferromagnetic aneurysm clips are considered a contraindication to MR imaging. Nonferromagnetic or weakly ferromagnetic aneurysm clips such as those of titanium alloy or pure titanium have been shown to be MR compatible and safe. Similar ferromagnetic objects may pose a risk of adverse effects including magnetically induced movements resulting in dislodgement and injury to organs, current, and heating. Of secondary concern is the fact that the ferromagnetic materials can produce image artifacts, thereby degrading the image quality.

Conventional Cerebral Angiography

In conventional angiography, a flexible catheter is introduced through the right femoral artery to visualize the intracranial arteries. Other less commonly used sites for access include left femoral artery, axillary, and brachial artery. Mild intravenous sedation improves patient comfort and cooperation, and reduces anxiety. The clinical question and disease process generally determines which vessels need to be examined. Routinely a four-vessel angiogram is performed, in which bilateral internal carotid and vertebral arteries are investigated. In a six-vessel angiogram, both external carotid arteries are also studied. The cerebral vasculature is visualized by injecting an iodinated contrast agent into these arteries and subsequently performing digital subtraction angiography (DSA), in which bony details are subtracted from a “mask” image, thus leaving us with images of different vessels. Serial fluoroscopic spot images are obtained throughout the procedure and standard angiographic views of the vessel of interest, including antero-posterior, lateral, and, if needed, oblique, are obtained. This principle can be extended for application in endovascular surgery, where cerebral angiographic techniques can not only be of diagnostic value, but also provide a route for endovascular therapy in entities such as cerebral aneurysms, arteriovenous malformation, and tumor embolization.

Cerebral angiography is considered to be the gold standard for the evaluation of cerebrovascular diseases. But it is an invasive procedure with the associated procedural risk of neurological complications—0.3–1.3%, of which 0.07–0.5% are permanent complications. ^, The majority of these complications are minor and transient including groin hematomas, femoral artery injury, and minor allergic reactions. However, more severe complications occasionally occur, such as cerebral infarction, seizure, and death. Spinal angiography poses the same risks as cerebral angiography, with the added danger of cord infarction secondary to spinal artery embolus. For this reason, spinal angiography should only be performed when a vascular malformation is demonstrated by another imaging modality or when the patient has SAH with normal cerebral angiography and a spinal source is strongly suspected. With improvements in the detection rates of cerebrovascular disease with newer, relatively noninvasive modalities such as CT angiography (CTA) or MR angiography (MRA), conventional catheter-based DSA has been replaced by CTA or MRA in some centers as the screening and diagnostic tool for intracranial vascular disease.

Magnetic Resonance Angiography and Computed Tomography Angiography

MRA is noninvasive and offers the opportunity to accurately depict the intracranial vasculature from different angles using a variety of methods for obtaining angiographic data. Three different MRA techniques are routinely available: time- of-flight MRA (TOF MRA), phase-contrast MRA (PC MRA), and contrast-enhanced MRA (CE MRA). The simplest and most widely used approach, TOF MRA, relies on in-flow enhancement. Essentially, static tissue within a two- or three-dimensional slice gives a low signal due to the saturating effect of the long train of closely spaced excitation pulses used in forming the image. On flowing into the imaging volume, unsaturated blood appears hyperintense relative to the static surround. ^, Three-dimensional TOF MRA is recommended for arterial evaluation, and a two-dimensional TOF MRA technique for venous evaluation. The disadvantages of MRA include limited visualization of very small distal cortical or deep branches, and a dependence on flow or the patient’s cooperation. To better visualize the veins and small arterial branches, intravenous contrast enhanced MRA can be used, but with the disadvantages of increased cost, and superimposition of veins and of enhanced soft tissues.

Advances in multidetector row CT (MDCT) have facilitated the quick and accurate examination of the cerebral vasculature. CTA is widely available, with fast, thin-section, volumetric spiral CT images acquired during the injection of a time-optimized bolus of contrast material for vessel opacification. With modern multisection CT scanners, the entire region from the aortic arch up to the circle of Willis can be covered in a single data acquisition, with excellent, three-dimensional spatial resolution. Multiplanar reformatted images, maximum intensity projection images (MIP), and three-dimensional reconstructions of axial CTA source images combine to provide images comparable, or even superior, to those obtained with conventional angiography ( Fig. 5.1 ).

A 26-year-old female who presented with sudden-onset severe headache. A, Noncontrast computed tomogtaphy (CT) of head shows diffuse subarachnoid hemorrhage, mainly in the anterior interhemispheric fissure with moderate hydrocephalus. B, Maximum intensity projection images reconstructed CT angiogram shows a lobulated anterior communicating artery aneurysm at right A1/A2 junction. C, Conventional catheter three-dimensional angiogram shows ruptured anterior communicating artery aneurysm, which was coiled successfully by two coils (D) in the same sitting.

Myelography and Computed Tomography Myelography

Myelography involves the injection of iodinated, water-soluble contrast material into the spinal subarachnoid space via a lumbar or, very rarely, a lateral C1–C2 puncture. Plain radiographs are obtained in multiple projections while the contrast is moved cranially or caudally to evaluate multiple levels. Better contrast agents and smaller-gauge spinal needles now permit myelography to be performed on an outpatient basis. After the study, the contrast agent is left in the subarachnoid space, from which it is absorbed and excreted in the urine. Myelography is typically followed by immediate or delayed CT examination (CT myelography). Nonionic contrast agents have dramatically reduced the side effects and complications associated with myelography. The most common post-procedural complication is mild-to-severe headache with nausea and/or vomiting. Because contrast material lowers the seizure threshold, patients with a history of seizures should be studied cautiously and patients on medications known to lower the seizure threshold (eg, tricyclic antidepressants) are commonly instructed to stop taking the drug 3 days before the myelography, to allow adequate drug clearance.

A CT myelogram has all the features of routine CT, including better spatial resolution with the added benefit of radio-opaque contrast material outlining the spinal cord and nerve roots. Pathologic lesions appear as abnormal filling defects within the contrast column, and any cord enlargement or deviation from anatomic position is easily appreciated ( Fig. 5.2 ). Now, MRI has become the imaging spine modality of choice, superseding both myelography and CT myelography, for the evaluation of spine pathology. The capability for multiplanar imaging, the use of nonionizing radiation, and the ability to obtain a myelographic-like image without an intrathecal contrast injection all provide distinct advantages. But still, myelography is preferred by some surgeons and is better in many circumstances, including postsurgical cases where MR quality is severely degraded due to artifacts from hardware.

A 38-year-old male shows a right paracentral broad-based disc at C5–6 level causing moderate canal and right neural foraminal stenosis on conventional cervical myelogram lateral view (A) , computed tomography myelogram, sagittal (B) , coronal (C) and axial (D) reconstructed images.

Perfusion Computed Tomography

Based on the multicompartmental tracer kinetic model, dynamic perfusion CT imaging is performed by monitoring the first pass of an iodinated contrast agent bolus through the cerebral circulation ( Fig. 5.3 ). As the change in CT enhancement (in Hounsfield units, HU) is proportional to the concentration of contrast, perfusion parameters are calculated by deconvolution from the changes in the density–time curve for each pixel using mathematical algorithms based around the central volume principle: ^,

• 1.
  

  Mean transit time (MTT) indicates the time difference between the arterial inflow and venous outflow.

  
  
• 2.
  

  Time to bolus peak (TTP) indicates the time from the beginning of contrast material injection to the maximum (peak) concentration of contrast material within a region of interest.

  
  
• 3.
  

  Cerebral blood volume (CBV) indicates the volume of blood per unit of brain mass (normal range in gray matter, 4–6 mL/100 g).

  
  
• 4.
  

  Cerebral blood flow (CBF) indicates the volume of blood flow per unit of brain mass per minute (normal range in gray matter, 50–60 mL/100 g/min). The relationship between CBF and CBV is expressed by the equation CBF = CBV/MTT.

A patient who has fallen from a 6-m height, admitted with a Glasgow Coma Scale score of 9. Neurological examination in the emergency room revealed an asymmetry of tone and deep tendon reflex involving both right upper and lower limbs. Admission contrast-enhanced cerebral computed tomography (CT) demonstrated a displaced left parietal skull fracture, associated with a large cephalhematoma. A small left parieto-occipital epidural hematoma (white arrowhead) and a small contusion area (white star) could also be identified on the conventional CT images. Perfusion-CT (PCT) demonstrated a much wider area of brain perfusion compromise (white arrows), with involvement of the whole left temporal and parietal lobes, the latter showing increased mean transit time (MTT) and decreased cerebral blood flow (CBF) and volume (CBV). Thus, PCT afforded a better understanding of the neurological examination findings on admission than conventional CT.

The main advantage of perfusion-CT is its wide availability and quantitative accuracy. Its main limitation is its inability to image the whole brain, as it is limited to a 2–3 cm section of brain tissue per bolus. Now with the availability of 320-slice volumetric multimodal CT, it is possible to visualize dynamic changes in the blood flow of the entire brain.

Diffusion-weighted Magnetic Resonance Imaging and Diffusion Tensor Imaging

DWI is based on the measurement of the random (Brownian) motion of water molecules and detects the degree of mobility (or diffusibility) of water molecules within tissues. By introducing spatial magnetic field gradients, it is possible to obtain MR sequences that are sensitive to the diffusivity of water along a chosen direction, obtaining so-called DWI. From the ratio of DWI images acquired at different levels of diffusion sensitization (known as b-value), it is possible to compute a quantitative measure of mean diffusivity, known as the apparent diffusion coefficient (ADC). The ADC measures water diffusion and, therefore, often mirrors changes in the DWI signal. In areas of increased diffusion like vasogenic edema, DWI signal intensity is low, and there is an increase in ADC. In regions of restricted diffusion like cytotoxic edema, DWI signal intensity is increased, and the ADC signal decreases.

This technique is widely used in acute ischemic stroke in which reduced diffusion resulting in increased DWI signal and reduced ADC is seen before the onset of visible abnormalities on conventional MR imaging. ^, In the affected region, there is a temporal evolution from restricted diffusion (ie, cytotoxic edema in the acute stroke setting) to unrestricted diffusion (ie, vasogenic edema and encephalomalacia in the chronic setting). DWI is also used to study other CNS processes such as cerebral and spinal abscesses, epidermoid cysts, traumatic brain injury (TBI), ^, and studying brain maturation and development, especially the myelination process.

Water diffusion properties also play a role in DTI—a related imaging technique. Whereas gray matter is microstructurally compact with no directional preference, white matter bundles are arranged in a highly directional manner. For this reason, while water usually diffuses in all directions (meaning diffusion is isotropic) in the brain, water diffuses preferentially along white matter tracts rather than across them (meaning diffusion in white matter is anisotropic). A mathematical algorithm known as diffusion tensor is commonly used to model anisotropic diffusion in white matter. Fractional anisotropy (FA) maps can be created—FA index varies between 0 (representing a symmetrical anisotropic medium where there is no directionality of the diffusion, for instance in water) and 1 (representing maximum anisotropy). Also, directionally encoded color maps and three-dimensional tractography can be performed to visually display white matter tracts ( Fig. 5.4 ).

A 66-year-old female with multiple peripherally enhancing centrally necrotic lesions involving left frontal lobe, basal ganglia, temporal lobe, and left cerebral peduncle, which was proven to be glioblastoma multiforme, WHO grade IV. On diffusion tensor imaging (DTI), there is noted displacement of left frontal corona radiata fibers and corticospinal tract in left cerebral peduncle. The colors have standard directional encoding: red is left-right, blue is superior-inferior and green is antero-posterior.

Perfusion-weighted Magnetic Resonance Imaging

While DWI is most useful for detecting irreversibly infarcted tissue, PWI may be used to identify areas of reversible ischemia as well. PWI techniques rely either on an exogenous method of achieving perfusion contrast (ie, the administration of an MR contrast agent typically gadopentate dimeglumine [Gd-DTPA, Magnevist®]) or on an endogenous method, which uses an endogenous diffusible tracer to measure CBF by applying magnetic resonance pulses to tag in-flowing water protons. ^, PWI is most commonly applied as bolus tracking following the intravenous administration of a bolus of gadolinium contrast. The passage of the contrast agent through the brain capillaries causes a transient loss of signal because of the susceptibility (T2*) effects of the contrast agent. A hemodynamic time-signal intensity curve is produced with subsequent calculation of MTT, TTP, CBF, and CBV perfusion maps using the same principles as those underlying perfusion CT imaging ( Fig. 5.5 ). ^, PWI can also be performed using T1-weighted imaging, also following an injection of gadolinium contrast. This technique requires a longer acquisition, but can measure the permeability of the blood–brain barrier.

A 64-year-old male patient admitted with aphasia and right-body motor deficit. Admission magnetic resonance angiography shows a proximal stenosis of the left middle cerebral artery (MCA) (arrow). Diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps feature a focus of restricted diffusion in the deep territory of MCA (arrowheads) consistent with acute stroke. Time-to-peak (TTP) and mean transit time (MTT) maps demonstrate an extensive alteration of brain hemodynamics. The DWI–PWI mismatch is classically considered as a hallmark of tissue at risk or penumbra.

(Courtesy Dr. Salvador Pedraza, Girona, Spain.)

Brain perfusion can also be assessed using another MRI technique called arterial spin labeling (ASL) ( Fig. 5.6 ). This method does not use an exogenous contrast agent, but rather uses an endogenous diffusible tracer to measure perfusion parameters by applying MR pulses to magnetically labeled in-flowing water protons. With increasing computer processing speeds and the speed of processing involved, this method is being increasingly used in clinical settings moving slowly away from the domain of being a purely research tool. This method is especially useful in patients who cannot be administered with contrast due to renal failure.

A 57-year-old female who presented with left pronator drift and right gaze preference. She was found to have right middle cerebral artery territory infarct involving right basal ganglia and periventricular white matter on diffusion-weighted imaging (DWI) (A) and apparent diffusion coefficient (ADC) (B) maps. Time-of-flight magnetic imaging angiogram (C) showed abrupt cut-off of right middle cerebral artery in M1 segment. Arterial spin labelling (ASL) map (D) showed reduced perfusion in right MCA distribution.

Magnetic Resonance Spectroscopy

MRS allows noninvasive, in vivo assessment of brain metabolism. The physical basis of MRS is the chemical shift effect. It actually means that nuclei located in different molecular environments sense slightly different magnitudes of magnetic field, causing them to process at different rates. MRS provides plots or spectra of signal intensity, which is proportional to concentration, versus precession rate shift with respect to a reference, expressed in parts per million (ppm). Various biologically relevant metabolites can be identified based on subtly different resonant frequencies, which are a reflection of their specific chemical environment. These metabolites reflect aspects of neuronal integrity, energy metabolism, and cell membrane proliferation or degradation. In clinical practice, five major metabolites containing hydrogen nuclei (1H-MRS) are typically evaluated ( Fig. 5.7 ): ^,

• 1.
  

  Creatine/phosphocreatine (Cr/PCr), 3.04 ppm: Creatine and phosphocreatine are involved in cellular energy metabolism and ATP production. As creatine and phosphocreatine levels tend to be relatively constant in the normal brain, they are used as a reference metabolite with the concentrations of other metabolites expressed as the ratio of the peak areas compared with the creatine peak.

  
  
• 2.
  

  N-acetyl aspartate (NAA), 2.02 ppm: NAA is a cellular amino acid and is a neuronal marker and a measure of neuronal density and integrity. Reduced levels have been reported in a wide spectrum of conditions involving neuronal death or dysfunction, decreased neural metabolism, axonal/dendritic loss, reduced myelination. As most brain tumors are of non-neuronal origin, NAA is absent or greatly reduced, as it is with other insults to the brain such as infarction or demyelination that produce neuronal dysfunction or loss. A decrease in NAA has also been observed after head injury.

  
  
• 3.
  

  Choline (Cho), 3.24 ppm: Cho is a composite signal of choline compounds (glycerophosphocholine [GPC], phosphocholine [PC] and a small amount of free choline) and thus reflects total brain choline stores. Cho is a constituent of the phospholipid metabolism of cell membranes and reflects membrane turnover. A Cho increase is characteristic of brain tumors due to accelerated membrane turnover in rapidly dividing cancer cells.

  
  
• 4.
  

  Lactate (Lac), 1.33 ppm: Under normal conditions, lactate is barely detectable by MRS in the normal healthy brain. Increased lactate production occurs in disorders of energy metabolism and suggests altered energy metabolism and is consistent with cerebral ischemia.

  
  
• 5.
  

  Glutamate and glutamine (Glx), composite peak between 2.1 and 2.5 ppm: Glutamate is an excitatory neurotransmitter that plays a role in mitochondrial metabolism. Gamma-aminobutyric acid is an important product of glutamate. Glutamine plays a role in detoxification and regulation of neurotransmitter activities. Elevated glutamate levels lead to excitotoxic cell damage. Increased glutamine synthesis occurs as a result of increased blood ammonia levels.

1A, Normal long echo (TE = 288 msec) single voxel white matter spectrum demonstrating the N-acetyl aspartate (NAA), creatine (Cr) and choline resonances at 2.02, 3.02 and 3.22 parts per million (ppm), respectively. There is no evidence of lactate or lipid contributions at 0.9–1.3 ppm. 1B, Normal short echo (TE = 26 msec) single voxel white matter spectrum demonstrating the N-acetyl aspartate (NAA), creatine (Cr) and choline resonances at 2.02, 3.02 and 3.22 parts per million (ppm), respectively. Contributions from glutamine and glutamate (Glx) are seen as a complex set of peaks at 2.2–2.5 ppm. Primary resonant peaks of myo-inositol are present at 3.56 and 4.06 ppm.

Plain Radiographs

Though plain radiographs were used for a lot of neurodiagnostic work, especially trauma patients, the advent of multiplanar imaging techniques, mainly CT and MRI, has relegated that role to the confines of history. Skull or spine radiographs can detect fractures; however, sensitivity is less than that of CT and intracranial and intraspinal injury cannot be as accurately evaluated by plain radiographs. Besides trauma, one practical use for skull radiographs which is still used in present settings is to exclude metallic foreign body in orbits prior to MRI.

Computed Tomography

It is not wrong to say that CT is the workhorse of a modern neurodiagnostic imaging facility, especially in emergent settings. Its widespread availability and short scan time make it the preferred imaging modality for initial evaluation of many intracranial lesions. The short scan time makes it especially useful in the settings of stroke and trauma in agitated, unstable patients who can benefit tremendously from the early detection of and neurosurgical intervention in incidences such as intracranial hemorrhage, hydrocephalus, and impending herniation. The early detection prompts early surgical intervention, which has been documented as improving patient outcomes. This has resulted in the increased utilization of CT scans in emergency departments over the last decade. Another advantage is volumetric data acquisition, which helps in better evaluation of intracranial and spinal structures in three dimensions. The principal disadvantage of CT is the ionizing radiation exposure, which has prompted, among other things, a campaign among clinicians and radiologists, the “Image Gently” campaign, to popularize a means of reducing the radiation dose in pediatric settings. One of the other disadvantages of CT is its inability to assess lesions in areas such as the posterior fossa and the floor of the middle cranial fossa due to “beam hardening” artifacts resulting from the attenuation of the X-ray beam behind relatively dense structures such as the clivus and temporal bone. Contrast agents commonly used in CT are iodine-based, the majority now being nonionic, resulting in lesions being more conspicuous due to breakdown of the blood–brain barrier.

Magnetic Resonance Imaging

MRI is increasingly being used for the delineation of details of the anatomy and also of complex lesions of the central nervous system. It uses the signals emitted by the relaxation of ubiquitous hydrogen nuclei present in water after they have been excited by radiofrequency pulses in a strong magnetic field. By varying the different pulse sequences in obtaining images, the soft tissue contrast of visualized anatomical structures can be varied. On T1-weighted images, fat appears bright and water and cerebrospinal fluid (CSF) appear black. On T2-weighted images, fat has intermediate signal appearing gray, while water and CSF appear bright. Cortical bone, composed of relatively fixed protons, does not produce a signal. Flowing blood produces no signal resulting in a so-called “signal void.” In general, pathologic processes usually contain excess amounts of free water and therefore are dark on T1-weighted images and bright on T2-weighted images. Hence, the rule of thumb is that anatomy is better seen on T1-weighted and pathology better on T2-weighted sequences. Contrast agents in the majority of cases are paramagnetic (eg, gadolinium-DTPA) and result in vessels and pathologic lesions being more conspicuous due to an increased T1 signal. This is the reason that post-contrast sequences are T1-weighted.

Different pulse sequences can be used for different types of CNS lesions. One of the commonest sequences to be used in all brain MRIs is the DWI sequence, which is particularly helpful in detecting early ischemia. This we shall discuss further in the functional neuroimaging section. Fluid-attenuated inversion recovery (FLAIR) sequence increases the conspicuity of focal hyperintense T2 signal in pathologic lesions by eliminating (or “nulling”) the hyperintense CSF signal. Thus, focal bright gray matter abnormalities in contusions or white matter abnormalities in diffuse axonal injuries (DAI) or multiple sclerosis are more easily appreciated against the adjacent “nulled” dark CSF spaces. FLAIR also has increased sensitivity for the presence of acute or subacute subarachnoid hemorrhage (SAH), which appears as a hyperintense signal within the sulci and cisterns. The gradient-echo (GRE) T2*-weighted MR sequence shows increased sensitivity for detection of intracranial blood. However, susceptibility-weighted imaging (SWI) has now proven to be more sensitive and better in detecting hemorrhage and calcification.

Magnetic resonance safety protocols and extensive pre-procedural screening are needed for the safety of the patients with the increasing use of biomedical implants and devices. Cardiac pacemakers, intraocular metallic fragments, mechanical device implants such as cochlear implants, drug infusion pump, neurostimulators for deep brain stimulation, and ferromagnetic aneurysm clips are considered a contraindication to MR imaging. Nonferromagnetic or weakly ferromagnetic aneurysm clips such as those of titanium alloy or pure titanium have been shown to be MR compatible and safe. Similar ferromagnetic objects may pose a risk of adverse effects including magnetically induced movements resulting in dislodgement and injury to organs, current, and heating. Of secondary concern is the fact that the ferromagnetic materials can produce image artifacts, thereby degrading the image quality.

Conventional Cerebral Angiography

In conventional angiography, a flexible catheter is introduced through the right femoral artery to visualize the intracranial arteries. Other less commonly used sites for access include left femoral artery, axillary, and brachial artery. Mild intravenous sedation improves patient comfort and cooperation, and reduces anxiety. The clinical question and disease process generally determines which vessels need to be examined. Routinely a four-vessel angiogram is performed, in which bilateral internal carotid and vertebral arteries are investigated. In a six-vessel angiogram, both external carotid arteries are also studied. The cerebral vasculature is visualized by injecting an iodinated contrast agent into these arteries and subsequently performing digital subtraction angiography (DSA), in which bony details are subtracted from a “mask” image, thus leaving us with images of different vessels. Serial fluoroscopic spot images are obtained throughout the procedure and standard angiographic views of the vessel of interest, including antero-posterior, lateral, and, if needed, oblique, are obtained. This principle can be extended for application in endovascular surgery, where cerebral angiographic techniques can not only be of diagnostic value, but also provide a route for endovascular therapy in entities such as cerebral aneurysms, arteriovenous malformation, and tumor embolization.

Cerebral angiography is considered to be the gold standard for the evaluation of cerebrovascular diseases. But it is an invasive procedure with the associated procedural risk of neurological complications—0.3–1.3%, of which 0.07–0.5% are permanent complications. ^, The majority of these complications are minor and transient including groin hematomas, femoral artery injury, and minor allergic reactions. However, more severe complications occasionally occur, such as cerebral infarction, seizure, and death. Spinal angiography poses the same risks as cerebral angiography, with the added danger of cord infarction secondary to spinal artery embolus. For this reason, spinal angiography should only be performed when a vascular malformation is demonstrated by another imaging modality or when the patient has SAH with normal cerebral angiography and a spinal source is strongly suspected. With improvements in the detection rates of cerebrovascular disease with newer, relatively noninvasive modalities such as CT angiography (CTA) or MR angiography (MRA), conventional catheter-based DSA has been replaced by CTA or MRA in some centers as the screening and diagnostic tool for intracranial vascular disease.

Magnetic Resonance Angiography and Computed Tomography Angiography

MRA is noninvasive and offers the opportunity to accurately depict the intracranial vasculature from different angles using a variety of methods for obtaining angiographic data. Three different MRA techniques are routinely available: time- of-flight MRA (TOF MRA), phase-contrast MRA (PC MRA), and contrast-enhanced MRA (CE MRA). The simplest and most widely used approach, TOF MRA, relies on in-flow enhancement. Essentially, static tissue within a two- or three-dimensional slice gives a low signal due to the saturating effect of the long train of closely spaced excitation pulses used in forming the image. On flowing into the imaging volume, unsaturated blood appears hyperintense relative to the static surround. ^, Three-dimensional TOF MRA is recommended for arterial evaluation, and a two-dimensional TOF MRA technique for venous evaluation. The disadvantages of MRA include limited visualization of very small distal cortical or deep branches, and a dependence on flow or the patient’s cooperation. To better visualize the veins and small arterial branches, intravenous contrast enhanced MRA can be used, but with the disadvantages of increased cost, and superimposition of veins and of enhanced soft tissues.

Advances in multidetector row CT (MDCT) have facilitated the quick and accurate examination of the cerebral vasculature. CTA is widely available, with fast, thin-section, volumetric spiral CT images acquired during the injection of a time-optimized bolus of contrast material for vessel opacification. With modern multisection CT scanners, the entire region from the aortic arch up to the circle of Willis can be covered in a single data acquisition, with excellent, three-dimensional spatial resolution. Multiplanar reformatted images, maximum intensity projection images (MIP), and three-dimensional reconstructions of axial CTA source images combine to provide images comparable, or even superior, to those obtained with conventional angiography ( Fig. 5.1 ).

A 26-year-old female who presented with sudden-onset severe headache. A, Noncontrast computed tomogtaphy (CT) of head shows diffuse subarachnoid hemorrhage, mainly in the anterior interhemispheric fissure with moderate hydrocephalus. B, Maximum intensity projection images reconstructed CT angiogram shows a lobulated anterior communicating artery aneurysm at right A1/A2 junction. C, Conventional catheter three-dimensional angiogram shows ruptured anterior communicating artery aneurysm, which was coiled successfully by two coils (D) in the same sitting.

Myelography and Computed Tomography Myelography

Myelography involves the injection of iodinated, water-soluble contrast material into the spinal subarachnoid space via a lumbar or, very rarely, a lateral C1–C2 puncture. Plain radiographs are obtained in multiple projections while the contrast is moved cranially or caudally to evaluate multiple levels. Better contrast agents and smaller-gauge spinal needles now permit myelography to be performed on an outpatient basis. After the study, the contrast agent is left in the subarachnoid space, from which it is absorbed and excreted in the urine. Myelography is typically followed by immediate or delayed CT examination (CT myelography). Nonionic contrast agents have dramatically reduced the side effects and complications associated with myelography. The most common post-procedural complication is mild-to-severe headache with nausea and/or vomiting. Because contrast material lowers the seizure threshold, patients with a history of seizures should be studied cautiously and patients on medications known to lower the seizure threshold (eg, tricyclic antidepressants) are commonly instructed to stop taking the drug 3 days before the myelography, to allow adequate drug clearance.

A CT myelogram has all the features of routine CT, including better spatial resolution with the added benefit of radio-opaque contrast material outlining the spinal cord and nerve roots. Pathologic lesions appear as abnormal filling defects within the contrast column, and any cord enlargement or deviation from anatomic position is easily appreciated ( Fig. 5.2 ). Now, MRI has become the imaging spine modality of choice, superseding both myelography and CT myelography, for the evaluation of spine pathology. The capability for multiplanar imaging, the use of nonionizing radiation, and the ability to obtain a myelographic-like image without an intrathecal contrast injection all provide distinct advantages. But still, myelography is preferred by some surgeons and is better in many circumstances, including postsurgical cases where MR quality is severely degraded due to artifacts from hardware.

A 38-year-old male shows a right paracentral broad-based disc at C5–6 level causing moderate canal and right neural foraminal stenosis on conventional cervical myelogram lateral view (A) , computed tomography myelogram, sagittal (B) , coronal (C) and axial (D) reconstructed images.

Perfusion Computed Tomography

Based on the multicompartmental tracer kinetic model, dynamic perfusion CT imaging is performed by monitoring the first pass of an iodinated contrast agent bolus through the cerebral circulation ( Fig. 5.3 ). As the change in CT enhancement (in Hounsfield units, HU) is proportional to the concentration of contrast, perfusion parameters are calculated by deconvolution from the changes in the density–time curve for each pixel using mathematical algorithms based around the central volume principle: ^,

• 1.
  

  Mean transit time (MTT) indicates the time difference between the arterial inflow and venous outflow.

  
  
• 2.
  

  Time to bolus peak (TTP) indicates the time from the beginning of contrast material injection to the maximum (peak) concentration of contrast material within a region of interest.

  
  
• 3.
  

  Cerebral blood volume (CBV) indicates the volume of blood per unit of brain mass (normal range in gray matter, 4–6 mL/100 g).

  
  
• 4.
  

  Cerebral blood flow (CBF) indicates the volume of blood flow per unit of brain mass per minute (normal range in gray matter, 50–60 mL/100 g/min). The relationship between CBF and CBV is expressed by the equation CBF = CBV/MTT.

A patient who has fallen from a 6-m height, admitted with a Glasgow Coma Scale score of 9. Neurological examination in the emergency room revealed an asymmetry of tone and deep tendon reflex involving both right upper and lower limbs. Admission contrast-enhanced cerebral computed tomography (CT) demonstrated a displaced left parietal skull fracture, associated with a large cephalhematoma. A small left parieto-occipital epidural hematoma (white arrowhead) and a small contusion area (white star) could also be identified on the conventional CT images. Perfusion-CT (PCT) demonstrated a much wider area of brain perfusion compromise (white arrows), with involvement of the whole left temporal and parietal lobes, the latter showing increased mean transit time (MTT) and decreased cerebral blood flow (CBF) and volume (CBV). Thus, PCT afforded a better understanding of the neurological examination findings on admission than conventional CT.

The main advantage of perfusion-CT is its wide availability and quantitative accuracy. Its main limitation is its inability to image the whole brain, as it is limited to a 2–3 cm section of brain tissue per bolus. Now with the availability of 320-slice volumetric multimodal CT, it is possible to visualize dynamic changes in the blood flow of the entire brain.

Diffusion-weighted Magnetic Resonance Imaging and Diffusion Tensor Imaging

DWI is based on the measurement of the random (Brownian) motion of water molecules and detects the degree of mobility (or diffusibility) of water molecules within tissues. By introducing spatial magnetic field gradients, it is possible to obtain MR sequences that are sensitive to the diffusivity of water along a chosen direction, obtaining so-called DWI. From the ratio of DWI images acquired at different levels of diffusion sensitization (known as b-value), it is possible to compute a quantitative measure of mean diffusivity, known as the apparent diffusion coefficient (ADC). The ADC measures water diffusion and, therefore, often mirrors changes in the DWI signal. In areas of increased diffusion like vasogenic edema, DWI signal intensity is low, and there is an increase in ADC. In regions of restricted diffusion like cytotoxic edema, DWI signal intensity is increased, and the ADC signal decreases.

This technique is widely used in acute ischemic stroke in which reduced diffusion resulting in increased DWI signal and reduced ADC is seen before the onset of visible abnormalities on conventional MR imaging. ^, In the affected region, there is a temporal evolution from restricted diffusion (ie, cytotoxic edema in the acute stroke setting) to unrestricted diffusion (ie, vasogenic edema and encephalomalacia in the chronic setting). DWI is also used to study other CNS processes such as cerebral and spinal abscesses, epidermoid cysts, traumatic brain injury (TBI), ^, and studying brain maturation and development, especially the myelination process.

Water diffusion properties also play a role in DTI—a related imaging technique. Whereas gray matter is microstructurally compact with no directional preference, white matter bundles are arranged in a highly directional manner. For this reason, while water usually diffuses in all directions (meaning diffusion is isotropic) in the brain, water diffuses preferentially along white matter tracts rather than across them (meaning diffusion in white matter is anisotropic). A mathematical algorithm known as diffusion tensor is commonly used to model anisotropic diffusion in white matter. Fractional anisotropy (FA) maps can be created—FA index varies between 0 (representing a symmetrical anisotropic medium where there is no directionality of the diffusion, for instance in water) and 1 (representing maximum anisotropy). Also, directionally encoded color maps and three-dimensional tractography can be performed to visually display white matter tracts ( Fig. 5.4 ).

A 66-year-old female with multiple peripherally enhancing centrally necrotic lesions involving left frontal lobe, basal ganglia, temporal lobe, and left cerebral peduncle, which was proven to be glioblastoma multiforme, WHO grade IV. On diffusion tensor imaging (DTI), there is noted displacement of left frontal corona radiata fibers and corticospinal tract in left cerebral peduncle. The colors have standard directional encoding: red is left-right, blue is superior-inferior and green is antero-posterior.

Perfusion-weighted Magnetic Resonance Imaging

While DWI is most useful for detecting irreversibly infarcted tissue, PWI may be used to identify areas of reversible ischemia as well. PWI techniques rely either on an exogenous method of achieving perfusion contrast (ie, the administration of an MR contrast agent typically gadopentate dimeglumine [Gd-DTPA, Magnevist®]) or on an endogenous method, which uses an endogenous diffusible tracer to measure CBF by applying magnetic resonance pulses to tag in-flowing water protons. ^, PWI is most commonly applied as bolus tracking following the intravenous administration of a bolus of gadolinium contrast. The passage of the contrast agent through the brain capillaries causes a transient loss of signal because of the susceptibility (T2*) effects of the contrast agent. A hemodynamic time-signal intensity curve is produced with subsequent calculation of MTT, TTP, CBF, and CBV perfusion maps using the same principles as those underlying perfusion CT imaging ( Fig. 5.5 ). ^, PWI can also be performed using T1-weighted imaging, also following an injection of gadolinium contrast. This technique requires a longer acquisition, but can measure the permeability of the blood–brain barrier.

A 64-year-old male patient admitted with aphasia and right-body motor deficit. Admission magnetic resonance angiography shows a proximal stenosis of the left middle cerebral artery (MCA) (arrow). Diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps feature a focus of restricted diffusion in the deep territory of MCA (arrowheads) consistent with acute stroke. Time-to-peak (TTP) and mean transit time (MTT) maps demonstrate an extensive alteration of brain hemodynamics. The DWI–PWI mismatch is classically considered as a hallmark of tissue at risk or penumbra.

(Courtesy Dr. Salvador Pedraza, Girona, Spain.)

Brain perfusion can also be assessed using another MRI technique called arterial spin labeling (ASL) ( Fig. 5.6 ). This method does not use an exogenous contrast agent, but rather uses an endogenous diffusible tracer to measure perfusion parameters by applying MR pulses to magnetically labeled in-flowing water protons. With increasing computer processing speeds and the speed of processing involved, this method is being increasingly used in clinical settings moving slowly away from the domain of being a purely research tool. This method is especially useful in patients who cannot be administered with contrast due to renal failure.

A 57-year-old female who presented with left pronator drift and right gaze preference. She was found to have right middle cerebral artery territory infarct involving right basal ganglia and periventricular white matter on diffusion-weighted imaging (DWI) (A) and apparent diffusion coefficient (ADC) (B) maps. Time-of-flight magnetic imaging angiogram (C) showed abrupt cut-off of right middle cerebral artery in M1 segment. Arterial spin labelling (ASL) map (D) showed reduced perfusion in right MCA distribution.

Magnetic Resonance Spectroscopy

MRS allows noninvasive, in vivo assessment of brain metabolism. The physical basis of MRS is the chemical shift effect. It actually means that nuclei located in different molecular environments sense slightly different magnitudes of magnetic field, causing them to process at different rates. MRS provides plots or spectra of signal intensity, which is proportional to concentration, versus precession rate shift with respect to a reference, expressed in parts per million (ppm). Various biologically relevant metabolites can be identified based on subtly different resonant frequencies, which are a reflection of their specific chemical environment. These metabolites reflect aspects of neuronal integrity, energy metabolism, and cell membrane proliferation or degradation. In clinical practice, five major metabolites containing hydrogen nuclei (1H-MRS) are typically evaluated ( Fig. 5.7 ): ^,

• 1.
  

  Creatine/phosphocreatine (Cr/PCr), 3.04 ppm: Creatine and phosphocreatine are involved in cellular energy metabolism and ATP production. As creatine and phosphocreatine levels tend to be relatively constant in the normal brain, they are used as a reference metabolite with the concentrations of other metabolites expressed as the ratio of the peak areas compared with the creatine peak.

  
  
• 2.
  

  N-acetyl aspartate (NAA), 2.02 ppm: NAA is a cellular amino acid and is a neuronal marker and a measure of neuronal density and integrity. Reduced levels have been reported in a wide spectrum of conditions involving neuronal death or dysfunction, decreased neural metabolism, axonal/dendritic loss, reduced myelination. As most brain tumors are of non-neuronal origin, NAA is absent or greatly reduced, as it is with other insults to the brain such as infarction or demyelination that produce neuronal dysfunction or loss. A decrease in NAA has also been observed after head injury.

  
  
• 3.
  

  Choline (Cho), 3.24 ppm: Cho is a composite signal of choline compounds (glycerophosphocholine [GPC], phosphocholine [PC] and a small amount of free choline) and thus reflects total brain choline stores. Cho is a constituent of the phospholipid metabolism of cell membranes and reflects membrane turnover. A Cho increase is characteristic of brain tumors due to accelerated membrane turnover in rapidly dividing cancer cells.

  
  
• 4.
  

  Lactate (Lac), 1.33 ppm: Under normal conditions, lactate is barely detectable by MRS in the normal healthy brain. Increased lactate production occurs in disorders of energy metabolism and suggests altered energy metabolism and is consistent with cerebral ischemia.

  
  
• 5.
  

  Glutamate and glutamine (Glx), composite peak between 2.1 and 2.5 ppm: Glutamate is an excitatory neurotransmitter that plays a role in mitochondrial metabolism. Gamma-aminobutyric acid is an important product of glutamate. Glutamine plays a role in detoxification and regulation of neurotransmitter activities. Elevated glutamate levels lead to excitotoxic cell damage. Increased glutamine synthesis occurs as a result of increased blood ammonia levels.

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