Diagnostic Methods A Individual Processes 1 Structural Anatomy

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a. Computed Tomography X-ray CT was the first noninvasive imaging technique that allowed for direct visulization of the brain parenchyma. It revolutionized the evaluation of patients with neurological and neurosurgical disorders because it could image bone and provided the first opportunity to see the brain directly. It has a small dynamic contrast range so that

Table II

Brain Mapping Methods of Use in the Study of Human Disease along with the Types of Measurements They Provide and Some of the Clinical

Situations in which They May Be of Use

Method

Measurements provided

Disorders

X-ray computed tomography (CT)

Magnetic resonance imaging

Positron emission tomography

Single photon emission computed tomography

Xenon-enhanced computed tomography

Helical computed tomography (CT angiography)

Electroencephalography

Magnetoencephalography Transcranial magnetic stimulation Optical intrinsic signal imaging

Brain structure Blood-brain barrier integrity

Brain structure Brain and cervical vasculature Relative cerebral perfusion Chemical concentrations Fiber tracts

Blood-brain barrier integrity

Perfusion Metabolism Substrate extraction Protein synthesis Neurotransmitter integrity Receptor binding Blood-brain barrier integrity

Perfusion

Neurotransmitter integrity Receptor binding Blood-brain barrier integrity Perfusion

Vascular anatomy Bony anatomy Electrophysiology

Electrophysiology Focal brain activation

Integrated measure of blood volume, metabolism, and cell swelling

Acute/chronic hemorrhages Acute trauma

General screening of anatomy Focal or generalized atrophy Hydrocephalus Acute ischemia Neoplasms

Demyelinating disease Epileptic foci Degenerative disorders Infections

Preoperative mapping Ischemic states Degenerative disorders Epilepsy

Movement disorders Affective disorders Neoplasms Addictive states Preoperative mapping Ischemic states

Degenerative disorders Epilepsy

Movement disorders Ischemic states

Vascular occulsive disease

Aneurysms

Arteriovenous malformations Epilepsy

Encephalopathics Degenerative disorders Preoperative mapping Epilepsy

Preoperative mapping Intraoperative mapping differentiation of gray and white matter is difficult (Fig. 1A). However, it is very sensitive for identifying cerebral hemorrhage and also lesions associated with an alteration in the blood-brain barrier, by virtue of leakage of iodinated contrast material in them. These abilities make X-ray CT ideal for direct and immediate assessment of patients with cerebral hemorrhage, multiple sclerosis, brain tumors, and traumatic

Brain Bleed Scan

Figure 1 X-ray CT. (A) Images of the human brain from an X-ray CT device, demonstrating good anatomical detail, particularly of the skull and ventricular system as well as the subarachnoid CSF spaces. Note that there is less gray-white contrast than in MRI images (Fig. 2A). (B) X-ray CT provided very detailed images of bony structures that surround the central nervous system. This is particularly useful in evaluating pathologic states at the base of the skull, where conventional radiography is often difficult because of patient positioning and the overlap of bony structures in a two-dimensional radiograph. Furthermore, in situations in which trauma is a factor, often patients cannot be manipulated easily because of the possibility of fractures at the base of the skull or in the cervical spine. (C) Intracerebral hemorrhage demonstrated by X-ray CT. Sensitivity for detection of intracranial bleeds is effectively 100% with X-ray CT and it remains the imaging modality of choice in acute patients when identification of cerebral hemorrhage is urgent and important. This is typically the case in patients with an acute cerebral deficit when cerebral hemorrhage must be identified if thrombolytic or anticoagulant therapy is being contemplated.

Figure 1 X-ray CT. (A) Images of the human brain from an X-ray CT device, demonstrating good anatomical detail, particularly of the skull and ventricular system as well as the subarachnoid CSF spaces. Note that there is less gray-white contrast than in MRI images (Fig. 2A). (B) X-ray CT provided very detailed images of bony structures that surround the central nervous system. This is particularly useful in evaluating pathologic states at the base of the skull, where conventional radiography is often difficult because of patient positioning and the overlap of bony structures in a two-dimensional radiograph. Furthermore, in situations in which trauma is a factor, often patients cannot be manipulated easily because of the possibility of fractures at the base of the skull or in the cervical spine. (C) Intracerebral hemorrhage demonstrated by X-ray CT. Sensitivity for detection of intracranial bleeds is effectively 100% with X-ray CT and it remains the imaging modality of choice in acute patients when identification of cerebral hemorrhage is urgent and important. This is typically the case in patients with an acute cerebral deficit when cerebral hemorrhage must be identified if thrombolytic or anticoagulant therapy is being contemplated.

injuries. Contrast sensitivity and the time needed for scanning have improved since X-ray CT was introduced, but with the advent of MRI technology many diagnostic studies that were formerly in the province of X-ray CT are now done with MRI. Nevertheless, X-ray CT continues to have an important role in resolving certain diagnostic questions and in particular patient circumstances.

X-ray CT has remained the imaging modality of choice for patients requiring urgent evaluation of suspected intracranial hemorrhage (Fig. 1C) and in patients with acute head trauma. In both these circumstances, the speed of the study and ease of patient access as well as availability of equipment are well matched to the ability of CT to evaluate such patients. X-ray CT is also the procedure of choice when evaluating abnormalities of bony structures of the head particularly the skull base (Fig. 1B). Lastly, patients who cannot tolerate MRI because of claustrophobia or implanted ferromagnetic or electronic devices or that need to be attached to ancillary equipment such as is frequently encountered in critical care situations are also best scanned by X-ray CT if structural information is needed for clinical evaluation.

b. MRI Magnetic resonance imaging is the structural imaging modality of choice in all other situations. Its superior spatial resolution and contrast range, particularly useful in differentiating gray and white matter, are but two features of MRI that make it

Structural Mri Segment

Figure 2 Magnetic resonance imaging. (A-D) Typical two-dimensional MRI images of the brain. Notice that the detailed anatomy of the brain parenchyma has better gray-white contrast than X-ray CT images (Fig. 1A). Notice also that there are none of the typical CT artifacts caused by the juxtaposition of dense bone and brain parenchymay. (A) Coronal view through the thalamus demonstrating the subnuclei of the thalamus, the mamillary bodies, and the internal, external, and extreme capsules as well as the two segments of the globus pallidus. Also note the detailed anatomy of the hippocampi. (B) Sagittal view demonstrating the colliculi of the midbrain, the midline of the thalamus, and the detailed anatomy of the midsagittal region of the cerebellum. (C) Sagittal view through the hippocampus and striatum. Note the fine bridges of gray matter between the caudate and the putamen. (D) Transverse section through the basal ganglia and upper midbrain. Note the periaque-ductal gray matter, the detailed anatomy ofthe hippocampi, and the bilateral flow voids produced by the presence of the lenticulostriate arteries in the posterior portion of the putamen. (E) Three-dimensional reconstruction with cutaway of an MRI data set demonstrating the kind of anatomical detail that can be provided with three-dimensional MR images (courtesy of Colin Holmes and colleagues, UCLA School of Medicine, Los Angeles). [A-D from Holmes et al. (1998). Enhancement of magnetic resonance images using registration for signal averaging. J. Computer Assisted Tomogr. 22(1), 139-152].

superior to CT for structural imaging (Fig. 2). The ability to image brain structures from any angle and avoidance of CT artifacts that result from soft tissue-dense bone boundaries in the field of view provide further arguments for the use of MRI in patients with cerebral disorders. This advantage is most notable in the posterior fossa, where artifacts from the dense petrous bones often obscure or obliterate relevant clinical information about the brain stem and cerebellum. Gadolinium and other paramagnetic contrast agents can be used with MRI to provide the ability to detect blood-brain barrier defects in a manner analogous to that used in X-ray CT with iodinated contrast agents.

2. Vascular Anatomy a. MR Angiography The observation that protons leaving the field of view reduce the local signal in MRI studies has led to an entire field of MR angiography and associated flow-based MRI techniques. The so-called flow void occurs in the vascular system when blood that encounters a radiofrequency pulse leaves the field of view of the scanner and the resultant energy is therefore emitted outside the field of view. The result is a loss of signal within the lumina of blood vessels. When partitular pulse sequences are utilized to optimize this effect, an image of vascular anatomy results. Like most angiographic procedures, the image depicts the contents of the blood vessel (within the lumen) as opposed to the blood vessel wall and associated structures. However, unlike conventional angiography, in which arterial, capillary, and venous phases are distributed in time and images of each phase can be produced independently, MRA provides a composite image of all medium-to large-diameter vessels, including arteries and viens.

Such studies have provided important opportunities for the evaluation of intracranial and cervical, medium and large vessels for abnormalities, including arter-iovenous malformations, aneurysms, and occlusive disease. Smaller caliber vessels still require conventional angiographic or helical CT evaluation for the assessment of disorders such as vasculitis.

b. Helical CT In this technique, also called spiral CT or CT angiography, conventional CT technology is modified to produce very rapid sequential images of the head by having the relationship between the patient and the X-ray tube/detector system traverse a helical course through the tissue. This process is rapid and so

Figure 3 Helical CT angiography. (A) The cerebral vasculature is superimposed on this cutaway view of the skull seen from above. Note the line detail provided for the vascular structures, including the circle of Willis, the anterior, middle, and posterior cerebral arteries, and many of their branches. The arrow indicates an aneurysm arising from the middle cerebral artery at the anterior edge of the middle cerebral fossa. (B) Close-up view of the aneurysm demonstrated in A. Note that in this three-dimensional reconstruction, it is possible to see all of the blood vessels that contribute to or arise from the aneurysmal sack (left). Unlike conventional angiography, where the overlap of the aneurysm and the parent or daughter vessels can be obscured because of the two-dimensional projection required in this technique, full three-dimensional images are possible with helical CT angiography. By digital reconstruction and rotation of the data set from helical CT, these complex and important relationships can be evaluated prior to surgery, whereas with conventional angiograms multiple view would be required and still may not provide a sufficiently detailed view of these relationships. In addition, multiple views obtained with conventional angiography expose the patient to additional radiation and contrast risks. In this case, the angular artery (arrow) arises from the aneurysm sack. Endovascular coil placement might lead to obstruction of this important vessel, thereby making such a patient a candidate for surgical rather than endovascular treatment of this lesion (courtesy of Pablo Villablanca, UCLA School of Medicine).

Figure 3 Helical CT angiography. (A) The cerebral vasculature is superimposed on this cutaway view of the skull seen from above. Note the line detail provided for the vascular structures, including the circle of Willis, the anterior, middle, and posterior cerebral arteries, and many of their branches. The arrow indicates an aneurysm arising from the middle cerebral artery at the anterior edge of the middle cerebral fossa. (B) Close-up view of the aneurysm demonstrated in A. Note that in this three-dimensional reconstruction, it is possible to see all of the blood vessels that contribute to or arise from the aneurysmal sack (left). Unlike conventional angiography, where the overlap of the aneurysm and the parent or daughter vessels can be obscured because of the two-dimensional projection required in this technique, full three-dimensional images are possible with helical CT angiography. By digital reconstruction and rotation of the data set from helical CT, these complex and important relationships can be evaluated prior to surgery, whereas with conventional angiograms multiple view would be required and still may not provide a sufficiently detailed view of these relationships. In addition, multiple views obtained with conventional angiography expose the patient to additional radiation and contrast risks. In this case, the angular artery (arrow) arises from the aneurysm sack. Endovascular coil placement might lead to obstruction of this important vessel, thereby making such a patient a candidate for surgical rather than endovascular treatment of this lesion (courtesy of Pablo Villablanca, UCLA School of Medicine).

arranged that it is coincident with the delivery of a bolus of iodinated contrast material into the cranial and cervical vessels from a peripheral vein. The resultant images are high-resolution depictions of the intracranial anatomy that can be reconstructed in three dimensions (Fig. 3A). Currently, limited information is available about the technique in terms of its clinical applications, but it is likely that there are circumstances in which it may be superior to conventional angiography. One of those is in the assessment of the local vascular anatomy of patients with aneurysms and arteriovenous malformations. In this case, conventional angiography, while high in spatial resolution, collapses the three-dimensional structure of such lesions into a two-dimensional projection. As such, the important relationship between aneurysm neck and a parent or daughter vessel may be difficult to ascertain or may require multiple intraarterial contrast injections and radiation exposure for the patient. Helical CT allows for a true three-dimensional reconstruction of local anatomy that can be manipu lated to assess such relationships in greater detail, while subjecting the patient to only a single radiation exposure and dose of iodinated contrast material (Fig. 3B). A similar situation exists when defining feeder vessels to arteriovenous malformations.

3. Blood Flow and Perfusion a. PET The assessment of cerebral perfusion (i.e., cerebral blood flow per volume of tissue) can be determined quantitatively with PET using 15O-labeled water, 11C-labeled butanol, and potentially other agents. These agents are freely diffusible and knowledge of the time-activity relationship of the tracer compound in arterial blood and the tissue concentration over time in the brain permits a calculation of cerebral perfusion with approximately 5 x 5 x 5-mm spatial resolution. These methods have been used extensively to evaluate increments in perfusion associated with underlying neuronal activity such as that

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