There are two additional functional imaging techniques that deserve brief mention: magnetoencephalography (MEG) and xenon-enhanced CT (Xe/CT).
Magnetoencephalography
MEG is a noninvasive method that uses supercon-ducting sensors to measure the neuromagnetic fields gen-erated by neuronal activation. These fields pass through the skull and scalp without distortion. Thus, this method provides data similar to those provided by standard elec-troencephalogram (EEG) technology but with fewer
arti-facts. Using computerized models to generate activation maps, MEG can be used to localize patterns of brain ac-tivity. The spatial resolution that can be achieved from MEG data is greater than that from EEG data. Like EEG, MEG directly measures neuronal activity in milli-seconds, unlike the other functional imaging techniques, all of which provide indirect measures of neuronal activ-ity. The ability of MEG to monitor rapid changes in neu-ronal activity makes it possible to separate components of a cognitive task, such as word reading.
MEG has been used to study numerous neuropsychi-atric conditions, including epilepsy and autism (Hurley et al. 2000; King et al. 2000; Lewine et al. 1999a). There have been small studies assessing use of MEG in TBI (Iwasaki et al. 2001; Lewine et al. 1999b). The prelimi-nary work in TBI suggests that MEG may become a use-ful modality for evaluation of TBI patients, especially if combined with other imaging technologies. At present, MEG is available as a research tool only in a few large centers because of the high cost of the technology.
Xenon-Enhanced Computed Tomography
Xe/CT combines anatomical and CBF imaging. Stable xenon gas is both radiodense and lipid soluble. It dissolves
in the blood and enters the brain parenchyma. Patients inhale a mixture of xenon gas and oxygen via a face mask (Figure 6–12). CT scans are acquired before, during, and sometimes after inhalation. The CBF calculation is based on the arrival of xenon at each standardized unit of brain measured (i.e., pixel) and the amount of xenon exhaled. In February of 2001, the historical FDA status of xenon as a
“grandfathered” X-ray contrast agent was withdrawn, thus halting its clinical use. As of this writing, the perti-nent FDA-required studies are in progress. It is hoped that xenon will be available again soon.
Xe/CT has several advantages over other functional imaging methods. Because of the rapid elimination of xe-non from the body, Xe/CT can be repeated every 15 min-utes as desired. It can provide functional imaging data for patients undergoing a standard structural CT scan at a rel-atively low cost (approximately $100 in addition to the cost of the standard CT). Xenon is nonradioactive, so the acqui-sition of the structural CT is the only radiation exposure required for the scan. The main drawback of Xe/CT is that patients may experience positive or negative changes in mood, either of which could be problematic, especially in neuropsychiatric populations. Nausea also occurs in some patients. Apnea is a rare and reversible side effect. Sedation may be needed for neuropsychiatric patients.
Xe/CT has been used primarily for the evaluation of cerebrovascular accidents, bleeds, and aneurysms (Kil-patrick et al. 2001; Latchaw 2004; Taber et al. 1999).
Some work has been done with TBI patients, including assessment of ischemic regions after TBI and prediction of prognosis based on metabolic and blood flow changes in severe TBI (Kelly et al. 1996; Kushi et al. 1999; Marion and Bouma 1991; von Oettingen et al. 2002; Zurynski et al. 1995). Thus, Xe/CT may provide important research contributions to the understanding of the pathophysiol-ogy of TBI in the future (Figures 6–13, 6–14, and 6–15).
Summary
Despite the promise of functional brain imaging as a nonin-vasive means for evaluation of traumatic brain injury (TBI), clinical use has not been fully demonstrated at this time.
Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have each demonstrated lesions not seen on structural scans, especially in mild TBI, although the clinical significance of this finding for an individual patient with TBI has not been convincingly shown. SPECT and PET may have some role in prediction of outcome, which is presently their most common clinical use. Their use for assessment of brain changes correlating with findings on neuropsy-F I G U R E 6 – 1 2 . Procedure for obtaining a
xenon-enhanced CT (Xe/CT) scan.
Normal clinical CT scans are acquired as the first stage in an Xe/
CT study. The patient then inhales a mixture of xenon gas and oxygen via a face mask (as illustrated in this figure) for several minutes. Xe/CT images are acquired during inhalation. Gener-ally, a solid headholder is used to minimize motion of the head.
Source. Picture courtesy of Diversified Diagnostic Products, Inc.
chological testing, behavioral symptoms, and progress in rehabilitation is unclear. Despite the superior resolution of PET, its higher cost makes it difficult to justify over SPECT in evaluation of most TBI cases.
Functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) are promising methods for study of TBI. Activation paradigms are re-quired for most fMRI work, so standardization of cogni-F I G U R E 6 – 1 3 . Xenon-enhanced CT.
Axial CT (top row) and xenon-enhanced CT (bottom row) images of blood flow in normal brain. Blue areas indicate lower perfusion, and red areas indicate higher perfusion (see color key to the right of the figure).
Source. Picture courtesy of Diversified Diagnostic Products, Inc.
F I G U R E 6 – 1 4 . Acute presentation of traumatic brain injury on xenon-enhanced CT.
Axial CT (top row) and xenon-enhanced CT (Xe/CT) (bottom row) images of blood flow after an acute brain injury. Blue areas indicate lower perfusion and red areas indicate higher perfusion (see color key to the right of the figure). Xe/CT was used in this case to adjust the ventilator settings to achieve optimal perfusion.
Source. Picture courtesy of Diversified Diagnostic Products, Inc.
tive tasks must occur if clinical studies are to become use-ful. MRS is emerging as an important tool for study of neuropathology at a cellular level. It may be capable of demonstrating pathological change after TBI even in pa-tients with normal structural scans. As with PET and SPECT, the clinical applicability of this information has yet to be established in TBI.
With all functional imaging modalities, caution must be used in the interpretation of scans of TBI patients with concomitant (possibly preexisting) neurological or psychiatric conditions. Blood flow and metabolic changes are also seen on functional imaging studies of this population. In all functional imaging modalities used to study TBI, there is a need for more controlled studies using standardized methods to evaluate imaging data. Comparison of modalities in a single study is also important, because it will help establish how the modal-ities can be complementary to one another. Receptor studies may be important in future TBI work. As new ligands are developed, enabling studies of different neu-rotransmitter systems, it may be possible to image dis-ruption of particular systems after TBI (e.g., dopamine transmission deficits) and to individualize treatment us-ing these data.
It is probable that the most significant contribution of functional imaging to the study of TBI will be in under-standing its pathophysiology. All of the modalities de-scribed in this chapter and many new ones still in devel-opment will contribute to knowledge of how cell injury and death occur in TBI. It is possible that this
informa-tion could lead to new treatments, such as neuroprotec-tive therapies that can be used immediately after TBI to minimize neuronal damage.
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