Neuroimaging is often used in clinical psychiatry to rule out medical and neurological conditions that can mimic psychiatric disease rather than for the diagnosis of specific psychiatric disorders. Indeed, no known primary psychiatric disorder can be definitively diagnosed on the basis of neuroimaging alone.1 Brain imaging can be grossly divided into 2 separate categories: structural imaging and functional imaging. Structural imaging uses modalities such as CT and MRI, whereas functional imaging modalities include positron emission tomography (PET), single-photon emission CT (SPECT), magnetic resonance spectroscopy (MRS), functional MRI (fMRI), and diffusion tensor MRI tractography (DT-MRI or DTI).
Traditionally, the structural and functional divide has fallen along the lines of clinical and research applications: structural imaging is involved in the former and functional imaging is concerned with the latter. However, with developing research, the applicability of functional modalities such as fMRI is continually expanding. In fact, it is not unreasonable to envision a time in which functional neuroimaging could yield critical information about a patient’s specific diagnosis or the likelihood of a patient responding to certain therapeutic interventions. This review discusses the indications for structural imaging in patients presenting with psychiatric symptoms. Following brief descriptions of currently available functional neuroimaging modalities, the clinical and research utility of functional neuroimaging in psychiatric populations is discussed.
INDICATIONS FOR STRUCTURAL IMAGING
To rule out comorbidities
One large analysis across diverse populations found evidence of cortical atrophy in 30% of psychiatric patients who underwent CT imaging.2 In another study of 253 patients who presented with psychiatric symptoms, 15% had a change in their treatment regimen as a result of undergoing a structural brain MRI.3 However, the question of whether and when it is worthwhile to image patients with psychiatric symptoms remains unresolved.
Multiple studies have attempted to establish guidelines for the indications for neuroimaging in psychiatry. In one study, the presence of focal neurological signs and advanced patient age were the only reliable predictors of abnormalities on imaging in psychiatric inpatients.4 Dougherty and Rauch1 have proposed guidelines for structural neuroimaging in psychiatric populations. They suggest imaging for patients with abrupt changes in mental status associated with 1 of 3 criteria:
• Age over 50.
• Abnormal findings on neurological examination.
• A history of significant head trauma.
They also include new-onset psychosis and new-onset delirium of unknown cause as criteria for neuroimaging. In addition, they recommend structural imaging before an initial course of electroconvulsive therapy.1
CT has the following advantages compared with MRI: faster acquisition time and no contraindications in patients who have metallic implants. However, in the absence of contraindications and strict time constraints, MRI is the preferred modality because it provides better differentiation of gray from white matter, better evaluation of white matter pathology, better overall spatial resolution, and better ability to detect pathology in the posterior fossa.
As a primary tool to diagnose psychiatric illness
Several reports have indicated mild structural abnormalities associated with neuropsychiatric diseases. MRI has been used in Alzheimer disease to establish volume loss in critical medial temporal lobe structures (such as the hippocampus and the entorhinal cortex), as well as to predict progression from mild cognitive impairment to Alzheimer disease.5,6
In schizophrenia, common structural changes include enlargement of the lateral and third ventricles and volume loss in the dorsolateral prefrontal cortex, the medial temporal lobe, the thalamus, and the superior temporal gyrus.7,8 There are less consistent findings of changes in cortical volume in patients with mood disorders. Despite the above discoveries, findings on structural imaging are too variable and nonspecific to be used in isolation to diagnose psychiatric disorders.
FUNCTIONAL NEUROIMAGING MODALITIES
PET can be used to assess cerebral blood flow and cerebral glucose metabolism and to characterize neurotransmitter receptors. This technology uses injected unstable isotopes (eg, 18F, 15O, 11C) that emit positrons, which, in turn, collide with electrons to produce gamma ray radiation. The PET scanners detect this gamma ray radiation and the resulting information is fed to a computer, which produces an image. A common tracer used to measure cerebral glucose metabolism is 18F fluorodeoxyglucose. 15O-labeled H2O or CO2 is the tracer traditionally used in the assessment of cerebral blood flow. In addition to its usefulness in assessing cerebral blood flow and metabolism, PET remains the gold standard in studies of neurotransmitter receptors and transporters. Several radioligands are available for PET characterization of different receptors, including dopamine, serotonin, benzodiazepine, and opioid receptors.
SPECT is used to image regional cerebral blood flow that reflects cerebral metabolic activity. Like PET, SPECT scanning uses radiation from unstable isotopes to construct images. Unlike PET, SPECT does not yield a direct measurement of cerebral glucose metabolism. In addition, because of the technical differences between positron emission and single-photon emission, SPECT has slightly poorer spatial resolution than PET.
fMRI uses MRI machines with specific acquisition parameters and higher-speed scanning to assess cerebral blood flow and cerebral blood volume. fMRI accomplishes this by detecting changes in the paramagnetic properties of hemoglobin. This technique produces blood oxygen level–dependent signals of blood flow that are tightly coupled with neuronal activity. fMRI has a slightly better spatial resolution and a far better temporal resolution than either PET or SPECT (Figure).
MRS uses special MRI acquisition parameters to quantify various chemical substances within select brain areas (or regions of interest). Traditional molecular signatures measured with MRS include N-acetylaspartate, creatine, choline, and lactate. The quantification of these chemicals and the quantification of the ratios of one chemical to another yield information that can be clinically useful. For example, N-acetylaspartate levels are a marker of neuronal integrity, lactate levels are a measure of anaerobic metabolism, and creatine and choline levels can be used to assess cellular membrane turnover. MRS has therefore been used in certain neurological conditions, such as multiple sclerosis, CNS lymphoma, and mitochondrial disorders. In psychiatry, recent research has made possible the assessment of drug concentrations in the brain (eg, lithium and fluoxetine) by MRS.9,10
DT-MRI uses yet another special set of MRI acquisition parameters to enable reconstruction of white matter tracts and assessment of white matter tract integrity.11 Clinically, this technology has been used to gauge the integrity of white matter pathways (eg, in patients with diffuse axonal injury). In research settings, DT-MRI can be used to anatomically map the trajectory of white matter bundles.
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